Early Detection Of Gastric Cancer Research Articles

Investigating FGFR2 gene as a blood-based epigenetic biomarker in gastric cancer.

Gastric adenocarcinoma is a prevalent form of cancer that often remains undetected in its early stages due to the lack of specific symptoms. This delayed diagnosis leads to poor clinical outcomes, underscoring the need for an effective and non-invasive method for early detection. Recent advances in cancer epigenetics have led to the identification of biomarkers that have the potential to revolutionize the early detection and monitoring of this disease. One such promising biomarker is the methylation of the FGFR2 promoter. This study aims to measure the methylation levels of a specific CpG site in the FGFR2 promoter gene in DNA extracted from blood leukocytes from patients with intestinal metaplasia, gastric cancer, and healthy control. The CpG site of the FGFR2 gene promoter was identified in its control region. Methylation alteration of the selected FGFR2 CpG site was determined through the (methylation-sensitive restriction enzyme) MSRE-qPCR. Genomic DNA was extracted from one hundred twenty-five participants. The normal group had mean methylation levels of 93.23 ± 4.929%, while the IM group had a level of 69.85 ± 27.15%. In GC patients, the levels varied, with 25.96 ± 18.98% in the intestinal type and 28.30 ± 16.07% in the diffuse type. The methylation levels in the IM and GC patients were significantly lower than those in the normal control group. However, no significant difference was observed between the methylation status of the intestinal type of GC and the diffuse type. The Receiver operating characteristic (ROC) curve analysis showed that FGFR2 CpG methylation levels in GC patients compared to normal controls had a high sensitivity of 100% and specificity of 100%, with a cut-off of < 74.25%; when GC patients were compared to IM patients, the sensitivity was 85%, and the specificity was 80%, with a cut-off < 44.45%. The potential of the FGFR2 methylation status as a non-invasive biomarker lies in its ability to be detected in blood leukocytes, which makes it a promising tool for the early detection of intestinal metaplasia and gastric cancer. This could significantly improve the detection and management of these gastric conditions.

Metachronous remnant gastric cancer after proximal gastrectomy.

260 Background: Proximal gastrectomy is frequently selected for early gastric cancer located at the upper third of the stomach. Annual postoperative endoscopy is considered to be useful for the early detection of metachronous remnant gastric cancer (MRGC). Despite that, we sometimes have also encountered cases that are not suitable for endoscopic resection (ER). The aim of this study is to identify the risk factors for the patients who developed MRGC after proximal gastrectomy, received annual endoscopy, but are not eligible for ER (non-ER). Methods: We retrospectively analyzed 191 patients who had received annual endoscopic surveillance after undergoing PG for cT1 gastric cancer at NCCH between 2006-2015. MRGCs were categorized into two groups: ER group and non-ER group. The remnant stomach was defined as three locations: pseudo-fornix (PF), corpus and antrum. Results: The median observation period was 73 (range 12-168) months. MRGC was observed in 29 cases with 32 lesions. ER was eligible for 20 lesions (ER group, 62.5%), but 12 were not (non-ER group, 37.5%). We compared the characteristics between of ER group and non-ER group in terms of sex, age (&gt;65 years), interval from the initial surgery (&gt;60months), the location (PF vs non-PF), and cross-sectional circumference (posterior wall vs. others). In both univariate and multivariate logistic regression analysis, only the location at PF was identified as a risk factor for non-ER group (OR 25.0, 95% CI: 1.8–339, p = 0.015). Among 12 lesions of the non-ER group, the location of PF was found in 6 (50%) lesions. As compared with MRGC at the non-PF, that at the PF (n = 6) was characterized by younger patients (57.5 (range 37-69) years vs. 69 (56-77) years), larger size (36 (7-57) mm vs. 9 (9-24) mm), deeper depth (MP or deeper; 5/6 vs. 0/6), more frequent undifferentiated-type histology (4/6 vs. 0/6) and frequent nodal metastasis (3/6 vs. 0/6). The interval to detect MRGC appears to be longer in the PF (78 (31-96) months than that of the non-PF (60 (31-96) months), but the difference was not statistically significant (p = 0.86). Then, we examined the visibility and the mucosal normality of the area developing MRGC in the annual follow-up endoscopy one year before the detection of MRGC (n =32). In 25 lesions at the non-PF, the visibility and the mucosal normality was secured in 21 (84%). while 5 PF lesions were difficult to observe (71.4%, p = 0.01) due to food residues in 4 (57%, p = 0.047) and insufficient expansion of the gastric mucosa in 4 (57%, p = 0.001). Conclusions: Detection of the MRGC at the PF at an early stage is crucial and challenging. With annual follow-up endoscopy, complete clearance and adequately extending the gastric mucosa could lead to the early detection of MRGC at the PF.

Efficacy of magnifying endoscopy combined with narrowband imaging in detection of early gastric cancer: a systematic evaluation and meta-analysis.

To systematically evaluate the diagnostic accuracy of magnifying endoscopy combined with narrowband imaging (ME-NBI) in detecting early gastric cancer (EGC) and to provide a scientific basis for its clinical utility. Literature published before May 2024 that utilized ME-NBI for diagnosing EGC was searched across PubMed, EMBASE, The Cochrane Library, Web of Science, and major Chinese databases. Included studies were cohort studies or randomized controlled trials, and their quality was assessed using the QUADAS-2 framework. Meta-analysis was conducted using Stata 17 software to calculate diagnostic indicators such as sensitivity, specificity, and area under the curve (AUC). Heterogeneity was explored through Spearman's correlation coefficient, I2 statistics, subgroup analysis, and meta-regression analysis. Publication bias was assessed with Deeks' funnel plot. Twenty studies involving 7,770 patients and 7,917 lesions were included. The pooled sensitivity of ME-NBI for diagnosing EGC was 0.86 (95% CI: 0.80-0.90), specificity was 0.92 (95% CI: 0.86-0.96), and the AUC was 0.94 (95% CI: 0.91-0.96), demonstrating high diagnostic accuracy. Subgroup analysis revealed lower sensitivity in multicenter studies. Excised samples had similar sensitivity to biopsy samples but differed in specificity. Publication bias was detected (P=0.01), but sensitivity analysis corrected for this, maintaining high combined sensitivity, specificity, and AUC. ME-NBI is a highly accurate and reliable diagnostic tool for EGC. Despite have some bias and heterogeneity, this was effectively addressed through sensitivity and subgroup analyses. ME-NBI should be considered a preferred method for EGC screening and diagnosis in clinical practice.

Cell-free DNA methylation profiles enable early detection of colorectal and gastric cancer

Cell-free DNA methylation profiles enable early detection of colorectal and gastric cancer

THE RESULTS OF THE JAPANESE GASTRIC CANCER ASSOCIATION MORPHOLOGICAL CLASSIFICATION ADAPTATION FOR THE KAZAKH POPULATION

Relevance: Gastric cancer is a heterogeneous group of malignant epithelial tumors arising from the cells of the gastric mucosa, one of the most common forms of malignant neoplasms in many countries of the world. But, despite repeated attempts, there are no convincing approaches to early large-scale (screening) detection technology for this form of cancer. This causes a high rate of late detection of advanced forms of gastric cancer in most countries of the world, a high one-year mortality rate of patients, and a low five-year survival rate. Currently, full screening for gastric cancer is carried out only in Japan, Korea, and China – countries with high incidence rates.&#x0D; The study aimed to was a retrospective analysis of literary data on the epidemiology of gastric cancer in the world, individual countries, but, above all, our own materials, summarized by specialists of the Joint Stock Company “Kazakh Research Institute of Oncology and Radiology” (JSC “KazNIIOiR”) on the situation with cancer stomach in Kazakhstan; analysis of information on the types and results of screenings for the early detection of gastric cancer in the world.&#x0D; Methods:For the analysis, we used available epidemiological indicators on GC from the specialized literature, data obtained from annual reporting forms No. 7, approved by the Ministry of Health of the Republic of Kazakhstan, in the country code (ICD 10 – C16), publications with statistical and analytical materials on Kazakhstan. Morbidity and mortality rates were calculated based on data from the Bureau of National Statistics of the Agency for Strategic Planning and Reforms of the Republic of Kazakhstan website on the average annual population by region of Kazakhstan.&#x0D; Results: A long-term decrease in the incidence and mortality from gastric cancer in Kazakhstan since 2021 has been replaced by a stable increase in the incidence of gastric cancer against the backdrop of a high frequency of advanced forms, relatively high mortality, and low fiveyear survival of patients. At the same time, there is experience in the world of certain approaches to screening the population for early detection of gastric cancer.&#x0D; Conclusion: The high morbidity of gastric cancer in most regions of the country in recent years requires the search and development of optimal forms of screening for its early detection; this will reduce mortality from gastric cancer and increase the five-year survival rate of patients.

GASTRIC CANCER: EPIDEMIOLOGY AND PROSPECTS FOR THE DEVELOPMENT AND IMPLEMENTATION OF INNOVATIVE TECHNOLOGIES FOR EARLY DETECTION AND TREATMENT

Relevance: Gastric cancer is a heterogeneous group of malignant epithelial tumors arising from the cells of the gastric mucosa, one of the most common forms of malignant neoplasms in many countries of the world. But, despite repeated attempts, there are no convincing approaches to early large-scale (screening) detection technology for this form of cancer. This causes a high rate of late detection of advanced forms of gastric cancer in most countries of the world, a high one-year mortality rate of patients, and a low five-year survival rate. Currently, full screening for gastric cancer is carried out only in Japan, Korea, and China – countries with high incidence rates.&#x0D; The study aimed to assess the epidemiologically disadvantaged regions of Kazakhstan for cancer to select optimal early detection techniques to improve the treatment results.&#x0D; Methods:For the analysis, we used available epidemiological indicators on GC from the specialized literature, data obtained from annual reporting forms No. 7, approved by the Ministry of Health of the Republic of Kazakhstan, in the country code (ICD 10 – C16), publications with statistical and analytical materials on Kazakhstan. Morbidity and mortality rates were calculated based on data from the Bureau of National Statistics of the Agency for Strategic Planning and Reforms of the Republic of Kazakhstan website on the average annual population by region of Kazakhstan.&#x0D; Results: A long-term decrease in the incidence and mortality from gastric cancer in Kazakhstan since 2021 has been replaced by a stable increase in the incidence of gastric cancer against the backdrop of a high frequency of advanced forms, relatively high mortality, and low fiveyear survival of patients. At the same time, there is experience in the world of certain approaches to screening the population for early detection of gastric cancer.&#x0D; Conclusion: The high morbidity of gastric cancer in most regions of the country in recent years requires the search and development of optimal forms of screening for its early detection; this will reduce mortality from gastric cancer and increase the five-year survival rate of patients.

THE RESULTS OF THE JAPANESE GASTRIC CANCER SOCIETY MORPHOLOGICAL&#x0D; CLASSIFICATION ADAPTATION FOR THE KAZAKH POPULATION

Relevance: Gastric cancer (GC) morbidity is growing in Kazakhstan every year. In 2022, 2 915 new GC cases were detected (15 per 100,000&#x0D; population), making GC the third most common cancer. The early detection rate of GC does not exceed 10-20%, and advanced forms of GC are&#x0D; over 40%. Mortality increases in the first year after the diagnosis (up to 40%).&#x0D; The best way of solving early detection of gastric cancer is carrying out diagnostics at the stage of pre-tumor stomach diseases. Timely diagnosis and treatment of surgical and borderline diseases of the upper gastrointestinal tract (metaplastic and dysplastic changes in the mucous&#x0D; ОРГАНИЗАЦИЯ ЗДРАВООХРАНЕНИЯ&#x0D; Онкология и Радиология Казахстана, №4 (70) 2023 17&#x0D; membrane of the esophagus, stomach, and duodenum and adenocarcinomas and early cancer arising against this background) are a complex&#x0D; medical and social problem.&#x0D; Endoscopic methods for diagnosing esophagus, stomach, and duodenum diseases are the most highly informative nowadays. However, precancerous changes (atrophy, metaplasia, and dysplasia) in conventional endoscopic examination may not have specific features. It is necessary&#x0D; to improve the results of endoscopic diagnosis. The chromoscopy method may be one of the methods used to identify precancerous pathology&#x0D; and GC methods.&#x0D; The study aimed to increase the efficiency of gastric cancer early detection by adapting the morphological classification of the Japanese&#x0D; Gastric Cancer Society (JGCA) for the Kazakh population.&#x0D; Methods: We conducted endoscopic studies of 500 residents of the Republic of Kazakhstan using chromoscopy and morphological studies of&#x0D; the biopsy obtained during endoscopic examination. These patients had digestive system problems but previously did not have a GC diagnosis.&#x0D; We formed the risk groups according to JGCA (editions 13th and 14th).&#x0D; Results: We identified 3(0.6%) morbidity of severe dysplasia according to the results of 500 patients’ biopsy samples morphological study.&#x0D; This morphological structure is classified as a well-differentiated adenocarcinoma. We recommended a surgical treatment for identified patients.&#x0D; Conclusion: The identified cases of obligate pre-cancer with an extremely high probability of degeneration into a malignant neoplasm&#x0D; prove the importance of using JGCA for the early diagnosis of gastric cancer and allow us to recommend the use of chromoscopy in stomach&#x0D; endoscopic examination.

GASTRIC CANCER: EPIDEMIOLOGY AND PROSPECTS FOR THE DEVELOPMENT&#x0D; AND IMPLEMENTATION OF INNOVATIVE TECHNOLOGIES FOR EARLY DETECTION&#x0D; AND TREATMENT

Relevance: Gastric cancer is a heterogeneous group of malignant epithelial tumors arising from the cells of the gastric mucosa, one of the&#x0D; most common forms of malignant neoplasms in many countries of the world. But, despite repeated attempts, there are no convincing approaches&#x0D; to early large-scale (screening) detection technology for this form of cancer. This causes a high rate of late detection of advanced forms of gastric cancer in most countries of the world, a high one-year mortality rate of patients, and a low five-year survival rate. Currently, full screening&#x0D; for gastric cancer is carried out only in Japan, Korea, and China - countries with high incidence rates.&#x0D; The study aimed was a retrospective analysis of literary data on the epidemiology of gastric cancer in the world, individual countries, but,&#x0D; above all, our own materials, summarized by specialists of the Joint Stock Company “Kazakh Research Institute of Oncology and Radiology”&#x0D; (JSC “KazNIIOiR”) on the situation with cancer stomach in Kazakhstan; analysis of information on the types and results of screenings for the&#x0D; early detection of gastric cancer in the world.&#x0D; Methods: For the analysis, we used available epidemiological indicators on GC from the specialized literature, data obtained from annual&#x0D; reporting forms No. 7, approved by the Ministry of Health of the Republic of Kazakhstan, in the country code (ICD 10 - C16), publications with&#x0D; statistical and analytical materials on Kazakhstan. Morbidity and mortality rates were calculated based on data from the Bureau of National&#x0D; Statistics of the Agency for Strategic Planning and Reforms of the Republic of Kazakhstan website on the average annual population by region&#x0D; of Kazakhstan.&#x0D; Results: A long-term decrease in the incidence and mortality from gastric cancer in Kazakhstan since 2021 has been replaced by a stable&#x0D; increase in the incidence of gastric cancer against the backdrop of a high frequency of advanced forms, relatively high mortality, and low fiveyear survival of patients. At the same time, there is experience in the world of certain approaches to screening the population for early detection&#x0D; of gastric cancer.&#x0D; Conclusion: The high morbidity of gastric cancer in most regions of the country in recent years requires the search and development of&#x0D; optimal f

Robust Glycoproteomics Platform Reveals a Tetra-Antennary Site-Specific Glycan Capping with Sialyl-Lewis Antigen for Early Detection of Gastric Cancer.

The lack of efficient biomarkers for the early detection of gastric cancer (GC) contributes to its high mortality rate, so it is crucial to discover novel diagnostic targets for GC. Recent studies have implicated the potential of site-specific glycans in cancer diagnosis, yet it is challenging to perform highly reproducible and sensitive glycoproteomics analysis on large cohorts of samples. Here, a highly robust N-glycoproteomics (HRN) platform comprising an automated enrichment method, a stable microflow LC-MS/MS system, and a sensitive glycopeptide-spectra-deciphering tool is developed for large-scale quantitative N-glycoproteome analysis. The HRN platform is applied to analyze serum N-glycoproteomes of 278 subjects from three cohorts to investigate glycosylation changes of GC. It identifies over 20000 unique site-specific glycans from discovery and validation cohorts, and determines four site-specific glycans as biomarker candidates. One candidate has branched tetra-antennary structure capping with sialyl-Lewis antigen, and it significantly outperforms serum CEA with AUC values > 0.89 compared against < 0.67 for diagnosing early-stage GC. The four-marker panel can provide improved diagnostic performances. Besides, discrimination powers of four candidates are also testified with a verification cohort using PRM strategy. This findings highlight the value of this strong tool in analyzing aberrant site-specific glycans for cancer detection.

Deep Learning and Gastric Cancer: Systematic Review of AI-Assisted Endoscopy.

Gastric cancer (GC), a significant health burden worldwide, is typically diagnosed in the advanced stages due to its non-specific symptoms and complex morphological features. Deep learning (DL) has shown potential for improving and standardizing early GC detection. This systematic review aims to evaluate the current status of DL in pre-malignant, early-stage, and gastric neoplasia analysis. A comprehensive literature search was conducted in PubMed/MEDLINE for original studies implementing DL algorithms for gastric neoplasia detection using endoscopic images. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The focus was on studies providing quantitative diagnostic performance measures and those comparing AI performance with human endoscopists. Our review encompasses 42 studies that utilize a variety of DL techniques. The findings demonstrate the utility of DL in GC classification, detection, tumor invasion depth assessment, cancer margin delineation, lesion segmentation, and detection of early-stage and pre-malignant lesions. Notably, DL models frequently matched or outperformed human endoscopists in diagnostic accuracy. However, heterogeneity in DL algorithms, imaging techniques, and study designs precluded a definitive conclusion about the best algorithmic approach. The promise of artificial intelligence in improving and standardizing gastric neoplasia detection, diagnosis, and segmentation is significant. This review is limited by predominantly single-center studies and undisclosed datasets used in AI training, impacting generalizability and demographic representation. Further, retrospective algorithm training may not reflect actual clinical performance, and a lack of model details hinders replication efforts. More research is needed to substantiate these findings, including larger-scale multi-center studies, prospective clinical trials, and comprehensive technical reporting of DL algorithms and datasets, particularly regarding the heterogeneity in DL algorithms and study designs.

3D Stochastic Microsensors for Simultaneous Assay of p53, HER-3, and HER-4 - a Key Factor in the Early Detection of Gastric Cancer

The present study reports on the characterization and validation of a 3D stochastic microsensor that utilizes nitrogen, and boron co-doped graphene for the simultaneous determination of p53, HER-3, and HER-4 in biological samples. The synthesis and morphological characterization of nitrogen, and boron co-doped graphene powder was conducted through the utilization of scanning electron microscopy and X-ray powder diffraction techniques. The utilization of the 3D stochastic microsensor based on nitrogen, and boron co-doped graphene for the assay of p53 demonstrated an increased sensitivity and an extended linear concentration range. The limits of quantification for all biomarkers tested were observed to be at the magnitude order of attogram ml−1. The outcomes derived from the application of the suggested stochastic microsensor demonstrated a significant association with biological samples, indicating the prospective dependability of this for screening examinations employed in the molecular identification and quantification of p53, HER-3, and HER-4 in samples of whole blood, gastric tissue tumors, saliva, and urine. The signatures of other biomarkers or substances found in biological samples were found to be higher than those of p53, HER-3, and HER-4, suggesting that the latter do not impede the measurements. The biomarkers demonstrate accurate identification in biological samples, achieving recoveries greater than 98.00% and RSD% values less than 0.05.

Inflammatory microenvironment in gastric premalignant lesions: implication and application.

Gastric precancerous lesions (GPL) are a major health concern worldwide due to their potential to progress to gastric cancer (GC). Understanding the mechanism underlying the transformation from GPL to GC can provide a fresh insight for the early detection of GC. Although chronic inflammation is prevalent in the GPL, how the inflammatory microenvironment monitored the progression of GPL-to-GC are still elusive. Inflammation has been recognized as a key player in the progression of GPL. This review aims to provide an overview of the inflammatory microenvironment in GPL and its implications for disease progression and potential therapeutic applications. We discuss the involvement of inflammation in the progression of GPL, highlighting Helicobacter pylori (H. pylori) as a mediator for inflammatory microenvironment and a key driver to GC progression. We explore the role of immune cells in mediating the progression of GPL, and focus on the regulation of inflammatory molecules in this disease. Furthermore, we discuss the potential of targeting inflammatory pathways for GPL. There are currently no specific drugs for GPL treatment, but traditional Chinese Medicine (TCM) and natural antioxidants, known as antioxidant and anti-inflammatory properties, exhibit promising effects in suppressing or reversing the progression of GPL. Finally, the challenges and future perspectives in the field are proposed. Overall, this review highlights the central role of the inflammatory microenvironment in the progression of GPL, paving the way for innovative therapeutic approaches in the future.

Endoscopic diagnosis and prevalence of early gastric cancer in India: A prospective study.

Although countries like Japan and South Korea have implemented nationwide endoscopic screening programs, there is limited evidence on the effectiveness of endoscopy for diagnosing early gastric cancer (EGC) in developing countries such as India. In the present study, we aimed to determine the feasibility of endoscopic detection of EGC from India. The data was prospectively collected for all patients ≥40 years who underwent a diagnostic upper endoscopy from April to September 2021. A single endoscopist who performed the endoscopic procedures completed 1-month training in advanced endoscopy in Japan. Following the training, the endoscopist continued to engage in internet-based discussions regarding his cases encountered. Prior to this training, the endoscopist had not detected any EGC cases during his 12-year gastroenterology practice. A total of 1033 patients were included in the study, with males accounting for 65.4% and a mean age 52 years. The average procedural time was 7.13±4.8min. A total of 25 patients (2.4%) were found to have GC, including 6 patients (0.6%) with EGC. Two patients had synchronous EGC lesions. All EGC patients were males, with an average age of 66 years. All EGCs were detected in the distal stomach in the presence of Helicobacter pylori infection and severe atrophic gastritis. Our findings showed that the endoscopic detection of EGC is feasible in India. Optimal training on endoscopic diagnosis of EGC can improve the detection of such lesion. Further studies are warranted to assess the optimization and implementation of an endoscopic screening program for EGC in India.

Gastric Cancer Prevention; Detection of Premalignant Gastric Lesions and Surveillance for Early Detection of Gastric Cancer in Low Incidence Countries

Gastric Cancer Prevention; Detection of Premalignant Gastric Lesions and Surveillance for Early Detection of Gastric Cancer in Low Incidence Countries

Evaluation of rs10811661 polymorphism in CDKN2A / B in colon and gastric cancer

One of the causes of colon and gastric cancer is the dysregulation of carcinogenic genes, tumor inhibitors, and micro-RNA. The purpose of this study is to apply rs10811661 polymorphism in CDKN2A /B gene as an effective biomarker of colon cancer and early detection of gastric cancer. As a result,400 blood samples, inclusive of 200 samples from healthy individuals and 200 samples (100 samples from intestinal cancer,100 samples from stomach cancer) from the blood of someone with these cancers, to determine the genotype of genes in healthful and ill people through PCR-RFLP approach and Allelic and genotypic tests of SPSS software. To observe the connection between gastric cancer and bowel cancer risk and genotypes, the t-student test for quantitative variables and Pearson distribution for qualitative variables have been tested and the results have been evaluated using the Chi-square test. The effects confirmed that the highest frequency of TT genotypes is in affected individuals and CC genotype is in healthful individuals. In addition, it confirmed that women were more inclined than men to T3 tumor invasion and most grade II and III colon cancers, and in older sufferers with gastric cancer, the grade of tumor tended to be grade I. Among genetic variety and rs10811661, with invasiveness, there is a tumor size and degree in the affected person. In summary, our findings suggest that the rs10811661 polymorphism of the CDKN2A / B gene is strongly associated with the occurrence of intestinal cancer and stomach is linked to its potential role as a prognostic biomarker for the management of bowel cancer and stomach.

Multidimensional Analysis of a Cell-Free DNA Whole Methylome Sequencing Assay for Early Detection of Gastric Cancer: Protocol for an Observational Case-Control Study.

Commonly used noninvasive serological indicators serve as a step before endoscope diagnosis and help identify the high-risk gastric cancer (GC) population. However, they are associated with high false positives and high false negatives. Alternative noninvasive approaches, such as cancer-related features in cell-free DNA (cfDNA) fragments, have been gradually identified and play essential roles in early cancer detection. The integrated analysis of multiple cfDNA features has enhanced detection sensitivity compared to individual features. This study aimed to develop and validate an assay based on assessing genomic-scale methylation and fragmentation profiles of plasma cfDNA for early cancer detection, thereby facilitating the early diagnosis of GC. The primary objective is to evaluate the overall specificity and sensitivity of the assay in predicting GC within the entire cohort, and subsequently within each clinical stage of GC. The secondary objective involved investigating the specificity and sensitivity of the assay in combination with possible serological indicators. This is an observational case-control study. Blood samples will be prospectively collected before gastroscopy from 180 patients with GC and 180 nonmalignant control subjects (healthy or with benign gastric diseases). Cases and controls will be randomly divided into a training and a testing data set at a ratio of 2:1. Plasma cfDNA will be isolated and extracted, followed by bisulfite-free low-depth whole methylome sequencing. A multidimensional model named Thorough Epigenetic Marker Integration Solution (THEMIS) will be constructed in the training data set. The model includes features such as the methylated fragment ratio, chromosomal aneuploidy of featured fragments, fragment size index, and fragment end motif. The performance of the model in distinguishing between patients with cancer and noncancer controls will then be evaluated in the testing data set. Furthermore, GC-related biomarkers, such as pepsinogen, gastrin-17, and Helicobacter pylori, will be measured for each patient, and their predictive accuracy will be assessed both independently and in combination with the THEMIS model. Recruitment began in November 2022 and will be ended in April 2024. As of August 2022,250 patients have been enrolled. The final data analysis is anticipated to be completed by September 2024. This is the first registered case-control study designed to investigate a stacked ensemble model integrating several cfDNA features generated from a bisulfite-free whole methylome sequencing assay. These features include methylation patterns, fragmentation profiles, and chromosomal copy number changes, with the aim of identifying the GC population. This study will determine whether multidimensional analysis of cfDNA will prove to be an effective strategy for distinguishing patients with GC from nonmalignant individuals within the Chinese population. We anticipate the THEMIS model will complement the standard-of-care screening and aid in identifying high-risk patients for further diagnosis. ClinicalTrial.gov NCT05668910; https://www.clinicaltrials.gov/study/NCT05668910. DERR1-10.2196/48247.

Clinical and Morphological Features of Dysplasia and Early Gastric Cancer in the Patients with Autoimmune Gastritis

Аim: to analyze a series of cases of dysplasia and early gastric cancer developed in patients with autoimmune gastritis (AIG), and to identify their clinical and morphological features.Materials and methods. The study included six cases of detection of early gastric cancer on the background of AIG. Four out of six patients underwent endoscopic treatment, and in three out of six cases patients underwent endoscopic mucosectomy with dissection in the submucosal layer. One patient underwent endoscopic surgery in 2017, he continues annual dynamic follow-up without signs of tumour recurrence. A female patient with type 1 neuroendocrine tumour and mild dysplasia is awaiting treatment.Results. In five out of six patients with AIG, the localization of lesions prevailed in the stomach body, while all detected tumours were early ones, and according to the immunophenotype — of a gastric type. The presented cases of tumours were not accompanied by hyperplasia of neuroendocrine cells directly in the area of the tumour itself, but only in the surrounding gastric mucosa. Additionally, several cases of early gastrointestinal stromal tumours were found, which were characterized by low proliferative activity and had small sizes.Conclusion. The predominance of pseudopyloric metaplasia in the surrounding mucosa allows us to consider pseudopyloric metaplasia as a potentially significant change in the gastric mucosa of patients with AIG that may precede the development of gastric cancer.

Umbrella systematic review of potential quality indicators for the detection of dysplasia and cancer at upper gastrointestinal endoscopy.

Background and study aims Upper gastrointestinal (UGI) endoscopy lacks established quality indicators. We conducted an umbrella systematic review of potential quality indicators for the detection of UGI cancer and dysplasia. Methods Bibliographic databases were searched up to December 2021 for systematic reviews and primary studies. Studies reporting diagnostic accuracy, detection rates or the association of endoscopy or endoscopist-related factors with UGI cancer or dysplasia detection were included. AMSTAR2 and JBI checklists were used to assess systematic review and primary study quality. Clinical heterogeneity precluded meta-analysis and findings are summarized narratively. Results Eight systematic reviews and nine primary studies were included. Image enhancement, especially narrow band imaging, had high diagnostic accuracy for dysplasia and early gastric cancer (pooled sensitivity 0.87 (95% CI 0.84-0.89) and specificity 0.97 (0.97-0.98)). Higher detection rates with longer endoscopy examination times were reported in three studies, but no difference was observed in one study. Endoscopist biopsy rate was associated with increased gastric cancer detection (odds ratio 2.5; 95% confidence interval [CI] 2.1-2.9). Early esophageal cancer (0.17% vs 0.14%, P =0.04) and gastric cancer (0.16% vs 0.12%, P =0.02) detection rates were higher with propofol sedation compared to no sedation. Endoscopies performed by trained endoscopists on dedicated Barrett's surveillance lists had higher detection rates (8% vs 3%, P <0.001). The neoplasia detection rate during diagnostic endoscopies for Barrett's esophagus was 7% (95% CI 4%-10%). Conclusions Image enhancement use, longer examination times, biopsy rate and propofol sedation are potential quality indicators for UGI endoscopy. Neoplasia detection rate and dedicated endoscopy lists are additional potential quality indicators for Barrett's esophagus.

Flexible endoscopic instrument for diagnosis and treatment of early gastric cancer.

Gastric cancer is a common cancer endangering human life and health worldwide. Early detection and diagnosis of gastric cancer that is normally performed by flexible endoscope can significantly improve the survival rate of patients. However, current endoscopic instruments have some problems, such as limitation of degrees of freedom (DOFs) and lack of surgical triangulation. Meanwhile, the lack of an intraoperative technique for the real-time evaluation of early gastric cancer is also a serious problem. To solve these problems, we have developed a dual-bending flexible endoscopic instrument for the diagnosis and treatment of early gastric cancer. This instrument has a compact structure with a maximum outer diameter of 3mm and an insertion length of 1220mm. It has 5 DOFs with a dual-bending function, which can form a surgical operation triangulation to easily perform the endoscopic procedure. Apart from the surgical forceps, the end of the instrument can be equipped with different endoscopic devices to meet the needs of diagnosis and treatment, such as endomicroscopic probes, electrosurgical knives, and laser ablation optical fibers. It is verified that the instrument can carry these devices to complete corresponding tasks, demonstrating the great potential of this instrument in clinical applications.

Gastric cancer: Neural networks, complex system analysis, statistics and computer modeling for best management.

37 Background: We examined factors of alive supersystems – gastric cancer (GC) patients (GCP) and cell ratio factors (CRF) significantly affecting GCP survival. CRF - ratio between cancer cells (CC) and blood cells subpopulations. Methods: We analyzed data of 799 consecutive GCP (T1-4N0-2M0) (age=57.1±9.4 years; tumor size=5.4±3.1 cm) radically operated (R0) and monitored in 1975-2023 (m=558, f=241; total gastrectomies (G)=173, distal G=461; proximal G=165; combined G=247 with resection of esophagus, pancreas, liver, duodenum, diaphragm, colon transversum, splenectomy, etc; only surgery-S=624, adjuvant chemoimmunotherapy-AT=175 (5-FU + thymalin/taktivin); T1=238, T2=220, T3=184, T4=157; N0=437, N1=109, N2=253, M0=799. Variables selected for prognosis study were input levels of 45 blood parameters, sex, age, TNMG, cell type, tumor size. Survival curves were estimated by the Kaplan-Meier method. Differences in curves between groups of GCP were evaluated using a log-rank test. Multivariate Cox modeling, discriminant analysis, clustering, SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine any significant dependence. Results: Overall life span (LS) was 2128.9±2300.3 days and cumulative 5-year survival (5YS) reached 58.4%, 10 years – 51.9%, 20 years – 39%, 30 years – 27.2%. 318 GCP lived more than 5 years (LS=4304.5±2290.6 days), 169 GCP – more than 10 years (LS=5919.5±2020 days). 290 GCP died because of GC (LS=651±347.2 days). Cox modeling displayed that GCP survival significantly depended on CRF: healthy cells/CC, erythrocytes/CC, monocytes/CC, phase transition (PT) in terms of synergetics early—invasive cancer; PT N0--N12, age, G1-3, hemorrhage time, ESS, sex, AT, prothrombin index, residual nitrogen. Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early—invasive cancer (rank=1); PT N0--N12 (2); healthy cells/CC (3), erythrocytes/CC (4), thrombocytes/CC (5), monocytes/CC (6), segmented neutrophils/CC (7), leucocytes/CC (8), lymphocytes/CC (9), stick neutrophils/CC (10), eosinophils/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0). Conclusions: 5-year survival of GCP after radical procedures significantly depended on: PT “early-invasive cancer”; PT N0--N12; CRF; blood cell circuit; biochemical factors; hemostasis system; AT; GC characteristics; GC cell dynamics; tumor localization; anthropometric data; surgery type. Best diagnosis and treatment strategies for GC are: 1) screening and early detection of GC; 2) availability of experienced abdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunotherapy for GCP with unfavorable prognosis.