High Incidence Of Gastric Cancer Research Articles

Postoperative body weight change and its influencing factors in patients with gastric cancer.

The high incidence and mortality of gastric cancer (GC) pose a significant threat to human life and health, and it has become an important public health challenge in China. Body weight loss is a common complication after surgical treatment in patients with GC and is associated with poor prognosis and GC recurrence. However, current attention to postoperative weight change in GC patients remains insufficient, and the descriptions of postoperative weight change and its influencing factors are also different. To investigate body weight changes in patients with GC within 6 mo after gastrectomy and identify factors that influence dynamic body weight changes. We conducted a prospective longitudinal study of 121 patients with GC and collected data before (T0) and 1 (T1), 3 (T2), and 6 (T3) mo after gastrectomy using a general data questionnaire, psychological distress thermometer, and body weight measurements. The general estimation equation (GEE) was used to analyze the dynamic trends of body weight changes and factors that influence body weight changes in patients with GC within 6 mo of gastrectomy. The median weight loss at T1, T2, and T3 was 7.29% (2.84%, 9.40%), 11.11% (7.64%, 14.91%), and 14.75% (8.80%, 19.84%), respectively. The GEE results showed that preoperative body mass index (BMI), significant psychological distress, religious beliefs, and sex were risk factors for weight loss in patients with GC within 6 mo after gastrectomy (P < 0.05). Compared with preoperative low-weight patients, preoperative obese patients were more likely to have weight loss (β = 14.685, P < 0.001). Furthermore, patients with significant psychological distress were more likely to lose weight than those without (β = 2.490, P < 0.001), and religious patients were less likely to lose weight 6 mo after gastrectomy than those without religious beliefs (β = -6.844, P = 0.001). Compared to female patients, male patients were more likely to experience weight loss 6 mo after gastrectomy (β = 4.262, P = 0.038). Male patients with GC with high preoperative BMI, significant psychological distress, and no religious beliefs are more likely to lose weight after gastrectomy.

High Incidence of Gastric Cancer in El Salvador: A National Multisectorial Study 2000-2014.

Gastric adenocarcinoma (GC) is the fourth leading cause of global cancer mortality, and leading infection-associated cancer. GC has significant geographic variability, with a high incidence in East Asia and mountainous regions of Latin America. In the U.S., GC represents a marked disparity with incidence rates that are 2-3 times higher in Hispanics compared to non-Hispanic whites. We conducted a national retrospective study of incident GC in El Salvador from to 2000-2014 to estimate the age-standardized incidence rate (ASIR) by using a combination of pathology and endoscopy databases. A unique multisectorial coalition was formed between the Ministry of Health (MINSAL) and ES Gastroenterology Society (AGEDES), representing public hospitals (n=5), governmental employee hospitals (ISSS, n=5), and private facilities (n=6), accounting for >95% of national endoscopy capacity. HER2 and EBV tumor status was ascertained in a representative sample during 2014-2016. 10,039 unique cases of GC were identified, 45.5% female, and mean age of 65. 21% and 9.4% were <55 and <45 years old, respectively. ASIRs (M, F) were 18.9 (95%CI;14.4-20.7) and 12.2 per 100,000 persons (95%CI;10.9-13.5), respectively, in the period 2010-2014 with all centers operational. Intestinal GC was 2.8 times more common than diffuse GC. 23.2% had partial or complete pyloric obstruction. The HER2 2+/3+ status was 16.7% and EBER positivity was 10.2%. A high incidence of gastric cancer was confirmed in El Salvador, and nearly half of patients were female. The findings have implications for cancer control in the Central America LMICs and for U.S. Latino populations.

High Incidence of Gastric Cancer in El Salvador: A National Multisectorial Study 2000-2014.

Gastric adenocarcinoma (GC) is the fourth leading cause of global cancer mortality, and leading infection-associated cancer. GC has significant geographic variability, with a high incidence in East Asia and mountainous regions of Latin America. In the U.S., GC represents a marked disparity with incidence rates that are 2-3 times higher in Hispanics compared to non-Hispanic whites. We conducted a national retrospective study of incident GC in El Salvador from to 2000-2014 to estimate the age-standardized incidence rate (ASIR) by using a combination of pathology and endoscopy databases. A unique multisectorial coalition was formed between the Ministry of Health (MINSAL) and ES Gastroenterology Society (AGEDES), representing public hospitals (n=5), governmental employee hospitals (ISSS, n=5), and private facilities (n=6), accounting for >95% of national endoscopy capacity. HER2 and EBV tumor status was ascertained in a representative sample during 2014-2016. 10,039 unique cases of GC were identified, 45.5% female, and mean age of 65. 21% and 9.4% were <55 and <45 years old, respectively. ASIRs (M, F) were 18.9 (95%CI;14.4-20.7) and 12.2 per 100,000 persons (95%CI;10.9-13.5), respectively, in the period 2010-2014 with all centers operational. Intestinal GC was 2.8 times more common than diffuse GC. 23.2% had partial or complete pyloric obstruction. The HER2 2+/3+ status was 16.7% and EBER positivity was 10.2%. A high incidence of gastric cancer was confirmed in El Salvador, and nearly half of patients were female. The findings have implications for cancer control in the Central America LMICs and for U.S. Latino populations.

Epidemiological profile of Ophir Loyola Cancer Hospital: A snapshot of the incidence of solid neoplasms in the eastern Amazon.

e22515 Background: The geographical distribution of cancer is a major concern in global public health, associated with this reality, the susceptibility of a population is closely linked to risk factors and carcinogenic profiles in different groups, which explain the heterogeneous prevalence and incidences among countries. In Brazil the region delimited by the Legal Amazon has a distinct epidemiological profile with a high prevalence of breast cancer and a low survival rate compared to countries with the highest human development index. Furthermore, the North and The Northeast has more than half of the country's penile cancer cases. In Pará, Ophir Loyola Cancer Hospital(OLCH) accounts for 71.11% of hospital visits in the state. The results of this study indicate the importance of OLCH as the reference center in Pará for the care and treatment of cancer patients. Methods: This was an ecological, exploratory, and mixed descriptive studythat investigated the epidemiological profile of patients with cancer treated at OLCH from January to December 2020. Sociodemographic data at admission were the primary variables, which were analyzed according to spatial distribution. Results: In this study, the data of 2952 patients were analyzed, with the majority being between the ages of 50 and 79 years (62.47%), and diagnosed but without previous treatment (87.30%). The most common cancers were breast (16.50%), cervical (13.40%), stomach (8.98%), and prostate (7.72%). The spatial distribution of the total number of cases, by the location of the primary solid tumor, was heterogeneous with regard to the number of cases per municipality. In Tucuruí Lake and Carajás, thyroid cancer was the second most frequent neoplasms, and in the Lower Amazon, it was the third most frequent . Previous studies have indicated the high mining activity in Carajás and the Lower Amazon with a strong relationship between methyl mercury and Mercury contamination in the Tapajós River and the adjacent gold extraction territory and and fish contamination. In some regions of Pará, cervical cancer is more prevalent than breast câncer in womans, which is different from the national data where it ranks second or third in the female population. Within the relationship between females and males, there was a higher proportion of cases of stomach cancer among men, representing the second more prevalent tumor in men, indicating a high incidence of gastric cancer in the region. Conclusions: The care profile at OLCH showed a high incidence of solid malignancies compared to other regions of Brazil, such as gastric cancer, cervical and thyroid cancer, indicating environmental and sociocultural influences on the carcinogenic profile present in the Eastern Amazon. Just as a heterogeneous incidence of tumors was seen in the regions of Pará.

Association of gastroesophageal reflux disease with gastritis activity in schoolchildren living in a region with a high incidence of gastric and esophageal cancer

Aim. To study the activity of the inflammatory process in the gastric mucosa (GM) in gastroesophageal reflux disease (GERD) in schoolchildren living in a region with a high incidence of stomach and esophageal cancer. Material and methods. The transverse method in the Republic of Tyva collected data on the presence of gastroenterological complaints in 1535 schoolchildren aged 7-17 years. The main diagnostic criterion for GERD was the presence of weekly heartburn in the subjects. Subsequently, esophagogastroduodenoscopy was performed with the taking of biopsy material of the mucosa of the antrum and body of the stomach in 246 children. Morphological assessment of GM was carried out in accordance with the Sydney classification after staining biopsy sections with hematoxylin-eosin. Diagnosis of Helicobacter pylori was carried out after staining according to Giemsa. The studies were approved by the ethics committee and the consent of the examined was obtained. Results. Schoolchildren in Tyva have a high prevalence of GERD (9.5%). Associative relationship of GERD with gastritis activity, both in the body (p=0.7338) and in the antrum (p=0.2036) was not revealed. In the antrum, the activity of gastritis was higher than in the body of the stomach (p=0.0001). In children with GERD, when infected with Helicobacter pylori, there was an increase in activity, both in the antrum (p=0.0001) and in the body of the stomach (p=0.0159). At the same time, in children with GERD, the inflammatory process is associated with infection by a microorganism, regardless of its belonging to the Cag A strain. Conclusion. An association of GERD with highly active Helicobacter pylori associated gastritis has been established, regardless of whether the microorganism belongs to the Cag A strain.

Epstein–Barr virus (Orthoherpesviridae: &lt;i&gt;Lymphocryptovirus&lt;/i&gt;) among Russian ethnic groups: Prevalence of EBV types (EBV-1 and EBV-2), &lt;i&gt;LMP1&lt;/i&gt; gene variants and malignancies

Introduction. The discovery of two EBV types (EBV-1 and EBV-2) has stimulated the study of their prevalence in populations and association with malignancies.&#x0D; Objective. To study the prevalence of EBV-1 and EBV-2 types among ethnic groups in Russia, to analyze PCR products of the LMP1 gene in virus isolates, and to evaluate the contribution of EBV types to the incidence of malignant neoplasms.&#x0D; Materials and methods. EBV isolates from oral lavages of the Republics Adygea, Kalmykia, Tatarstan and the Moscow Region (MR) representatives were studied by nested PCR for the belonging to EBV-1 and EBV-2 types. LMP1 amplicons obtained by real-time PCR from viral isolates DNA were classified and sequenced on an automatic DNA sequencer ABI PRISM 3100-Avant (USA). The sequencing results were analyzed using Chromas 230 and Vector NT programs (Invitrogen, USA). The reliability of the obtained data was assessed using statistical packages Statistica for Windows, 10.0.&#x0D; Results. The prevalence rates of EBV-1 and EBV-2 in representatives of four ethnic groups were compared with the incidence rates of some tumors in the population of three Republics and MR.&#x0D; The dominant persistence of the transforming in vitro EBV-1 type in representatives of the Republic of Tatarstan and MR correlated with a high incidence of gastric cancer and lymphomas in the population of these territories. On the contrary, predominant infection of the non-transforming in vitro EBV-2 type and both types of the virus in approximately the same percentage of representatives of Adygea and Kalmykia, respectively, correlated with a lower level incidence of above tumors in populations of these Republics. The differences between the incidence rates of neoplasms in the compared ethnic populations were statistically insignificant (p 0.05). LMP1 variants of viral isolates did not reflect either the level of EBV persistence types or the incidence of tumors.&#x0D; Conclusion. Infection of ethnic groups with EBV-1 and EBV-2 may vary significantly under the influence of various factors. The predominance of the in vitro transforming EBV-1 type in the population did not increase the incidence of tumors due to cases associated with the dominant virus type.

Association Between Vonoprazan and the Risk of Gastric Cancer After Helicobacter pylori Eradication

Potassium-competitive acid blockers (PCABs) have been increasingly used to treat upper gastrointestinal disorders, replacing proton pump inhibitors (PPIs). Whereas PPIs are associated with an increased risk of gastric cancer (GC) after Helicobacter pylori (Hp) eradication, it is uncertain whether PCABs carry the same risk. Using a population-based claims database in Japan, we identified patients who were prescribed a clarithromycin-based first regimen of Hp eradication between 2015 and 2018. Patients who failed this regimen and those diagnosed with GC before or within 1 year after Hp eradication were excluded. We compared GC incidence between PCAB users and histamine type-2 receptor antagonist (H2RA) users, matching them on the basis of propensity scores calculated with considerations for age, sex, smoking, alcohol consumption, comorbidities, and co-administered medications. PCABs included only vonoprazan in this study. Among 54,055 patients, 568 (1.05%) developed GC during the follow-up period (mean, 3.65 years). The cumulative incidence of GC was 1.64% at 3 years, 2.02% at 4 years, and 2.36% at 5 years in PCAB users and 0.71% at 3 years, 1.04% at 4 years, and 1.22% at 5 years in H2RA users. The use of PCABs was associated with a higher GC risk (matched hazard ratio, 1.92; 95% confidence interval, 1.13-3.25; P= .016). Longer PCAB use and high-dose PCAB use were significantly associated with higher incidence of GC. Sensitivity analyses showed the risk of GC incidence among PCAB users was comparable with that of PPI users. The use of PCABs was associated with an increased risk of GC among Hp-eradicated patients, with duration/dose response effects.

Staging of operative link on gastritis assessment and operative link on gastric intestinal metaplasia systems for risk assessment of early gastric cancer: a case–control study

AimsOperative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia assessment (OLGIM) systems are histological staging systems of gastritis for gastric cancer (GC) risk estimation. Intermediate OLGA/OLGIM...

Deep sequencing reveals recurrent somatic mutations and distinct molecular subgroups in gastric cancer in Mizo population, North East India

In India, Mizoram has the highest incidence of gastric cancer (GC) which might be associated with environmental factors such as diet, Helicobacter pylori (H.pylori) and Epstein-Barr virus (EBV) infections, and somatic genomic alterations. We performed PCR cum sequencing and fragment analysis for detection of H. pylori/EBV infection and microsatellite Instability (MSI) in GC patients (N = 68). Somatic mutations were identified by targeted and exome sequencing. We found 87% of GC patients infected with H. pylori and or EBV. Pathogenic infections were mostly mutually exclusive with only 16% of coinfection. TP53, MUC6, and ARID1A were significantly mutated. Two molecular subgroups with distinctive mutational profiles were identified: (1) patients harboring mutations in TP53 and (2) patients harboring mutations in RTK/RAS/PI3-K signaling pathway and chromatin-remodeling genes. Therefore, EBV and H. pylori infections and somatic mutations in the genes involved in RTK/RAS/PI3K signaling pathway, chromatin-remodeling, and TP53 might drive GC development and progression in Mizo patients.

Chinese expert consensus on the diagnosis and treatment of peritoneal metastasis of gastric cancer (2023 edition)

China is a country with a high incidence of gastric cancer, and the majority of patients are in the advanced stage. The peritoneum is the most common site of metastasis and recurrence in advanced gastric cancer. Attention to the standardized diagnosis and treatment of peritoneal metastases of gastric cancer is expected to significantly improve the prognosis and quality of life of some patients. Based on evidence-based medicine and the internationally accepted Delphi method, this consensus revises the Chinese expert consensus on the prevention and treatment of peritoneal metastasis of gastric cancer (2017 edition), reaches a preliminary consensus on the definition, classification, risk factors, diagnosis and prediction, grade assessment, prevention, treatment and management of complications of peritoneal metastasis of gastric cancer, and provides guidance for clinical work.

Esophagogastroduodenal Findings in Patients with Intraductal Papillary Mucinous Neoplasms.

The association between intraductal papillary mucinous neoplasms (IPMNs) and extra-pancreatic malignancies is controversial. This cross-sectional study compared esophagogastroduodenal findings in 340 IPMN patients to those of age- and gender-matched controls without known IPMNs who underwent esophagogastroduodenoscopies (EGDs) for similar clinical reasons. The presence of gastric and esophageal cancer, Barrett's esophagus, neuroendocrine tumors (NETs), gastrointestinal stromal tumors (GISTs), gastric adenomas, and ampullary tumors was assessed. The results showed that 4/340 (1.2%) of the IPMN patients had gastric cancer and 1/340 (0.3%) had esophageal cancer. The matched control group had a similar incidence of gastric cancer (5/340) (1.5%), with no esophageal cancer cases (p > 0.999). The overall incidence of other esophagogastroduodenal conditions did not significantly differ between the IPMN patients and the controls. However, the incidence of gastric cancer in the IPMN patients was higher than expected based on national cancer registry data (standardized incidence ratio of 31.39; p < 0.001; CI 8.38-78.76). In conclusion, IPMN patients have a significantly higher incidence of gastric cancer compared to the general population. However, the incidence of esophagogastroduodenal findings, including gastric and esophageal cancer, is similar between IPMN patients and those who undergo an EGD for similar clinical indications. Further research is needed to determine optimal surveillance strategies for IPMN patients regarding their risk of developing gastric cancer.

Galectin-3 and matrix metalloproteinases 2 and 9 in peripheral blood of gastric cancer patients

Background: High incidence of gastric cancer (GC), its aggressive clinical course, rapid tumor dissemination, low sensitivity to chemotherapy and lack of reliable laboratory diagnostic criteria urgently require a search for the most informative markers associated with key biologic properties of the tumors.&#x0D; Aim: Comparative analysis of galectin-3, matrix metalloproteinase (MMP)-2, and MMP-9 levels in peripheral blood of GC patients and healthy donors, assessment of association of these markers with clinical morphological characteristics of the disease, and prognosis of overall and relapse-free survival.&#x0D; Materials and methods: Sixty (60) primary treatment-nave GC patients (38 men, 22 women) aged 29 to 81 years and 90 healthy donors compatible with their age and sex were included into the study. Galectin-3 was measured in EDTA plasma, MMP-2 and MMP-9 in serum with standard direct enzyme immunoassay kits "Human MMP-2 (total)", "Human MMP-9 (total)", "Human Galectin-3" (RD Systems, USA).&#x0D; Results: Plasma galectin-3 concentration in the GC patients was significantly higher than in the healthy controls (median 12.9 and 10.6 ng/ml, respectively; p 0.0001). No difference in serum MMP-9 levels between GC patients and control subjects were found, while MMP-2 level in the control group was significantly higher, than in the GC patients (p = 0.039). No association between galectin-3, MMP-2, and MMP-9 blood levels in the GC patients could be identified. In contrast to GC patients, there was a positive correlation of plasma galectin-3 with age in the control group (rs = 0.51, p 0.005). No associations between the biomarkers levels in blood and clinical and morphological characteristics of GC were established, except MMP-9 being higher at Т4а invasion depth as compared to the earlier Т2 level. Marked differences in the overall survival depending on plasma galectin-3 levels were found, with the cut-off level of 12.9 ng/ml: the 5-year overall survival in the patients with low galectin-3 was better, than in those with its higher level (50 and 43%, respectively; however, the difference was non-significant, р 0.1). Both overall and relapse-free survival of the GC patients was higher in those with low ( 212 ng/ml) serum MMP-2: the 5-year overall survival in this group comprised 60% versus 23% in the patients with higher MMP-2 (p = 0.018). The difference in relapse-free survival was non-significant. Serum MMP-9 levels had no significant impact on the survival of GC patients.&#x0D; Conclusion: The ambiguous data on the clinical role of galectin-3, MMP-2, MMP-9 in GC obtained in this study indicate the necessity of further investigation of their possible utility for the diagnostics and prognosis of treatment results.

Abstract 6459: Developed and persistent dyslipidemia is associated with increased risk of gastric cancer in a prospective study

Abstract Background: Increasing evidence suggests that metabolic disorders are a risk factor for gastric cancer. However, there is a lack of evidence on whether changes and persistence of metabolic disorders affect the subsequent gastric cancer occurrence. Therefore, this study aimed to evaluate the effects of changes or persistence in metabolic syndrome and its components' status on the incidence of gastric cancer among Korean population. Methods: This study comprised 59,671 individuals from the Health Examinees Study who had baseline surveys from 2004 to 2012 and repeated measurements from 2012 to 2016; and were followed up until 2018. Metabolic syndrome and its components were defined according to the National Cholesterol Education Program Adult Treatment Panel III and modified based on Korean population criteria. Participants were categorized into free, developed, recovered, and persistent metabolic syndrome and its components. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for gastric cancer incidence using multivariable cox proportional hazard models with age as a time scale. Results: During the mean follow-up of 9.4 years, 312 subjects were newly diagnosed with gastric cancer. Compared with the metabolic syndrome-free group, the persistent group had a higher incidence of gastric cancer (HR 1.37, 95% CI 1.02-1.84). Among individual components, the developed-high triglycerides group had the highest gastric cancer incidence (HR 1.52, 95% CI 1.12-2.05), followed by the persistent group (HR 1.40, 95% CI 1.04-1.90) compared to the free group. The low HDL-cholesterol persistent group (HR 1.45, 95% CI 1.08-1.93) showed a higher incidence than in the free group. In the subgroup analysis, we found association between high triglycerides developed and gastric cancer in men, while for women, the associations were significant between high triglycerides and low HDL-cholesterol persistent groups and gastric cancer incidence. Conclusions: In this prospective cohort study, we found that developed or persistent dyslipidemia, assessed as abnormal triglycerides and low HDL-cholesterol, were associated with an increased incidence of gastric cancer. These findings suggest that effective management of dyslipidemia may reduce gastric cancer risk. Keywords: Gastric cancer, Dyslipidemia, Metabolic syndrome, Prospective cohort Citation Format: Dan Huang, Woo-Kyoung Shin, Katherine De la Torre, Sukhong Min, Aesun Shin, Jong-Koo Lee, Hyung-Ho Kim, Daehee Kang. Developed and persistent dyslipidemia is associated with increased risk of gastric cancer in a prospective study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6459.

Hereditary Diffuse Gastric Cancer

Hereditary diffuse gastric cancer (HDGC) is a dominantly inherited cancer syndrome characterized by a high incidence of diffuse gastric cancer (DGC) and lobular breast cancer (LBC). HDGC is caused by germline mutations in 2 genes involved in the epithelial adherens junction complex, CDH1 and CTNNA1. We discuss the genetics of HDGC and the variability of its clinical phenotype, in particular the variable penetrance of advanced DGC and LBC, both within and between families. We review the pathology of the disease, the mechanism of tumor initiation, and its natural history. Finally, we describe current best practice for the clinical management of HDGC, including emerging genetic testing criteria for the identification of new families, methods for endoscopic surveillance, the complications associated with prophylactic surgery, postoperative quality of life, and the emerging field of HDGC chemoprevention.

Disparities and outcomes in young adults admitted for gastric cancer in the US.

298 Background: Although global incidence of gastric cancer has been decreasing over the past decades, an upward trend has been reported in younger patients and certain ethnic groups over the past few years. The reason for this epidemiological trend is not fully understood, but differences in presentation and prognosis suggest that gastric cancer in the young might represent a different clinical entity. Here, we seek to identify differences in demographic characteristics and outcomes between young adults and older patients admitted for gastric cancer. Methods: Using the National Inpatient Sample (NIS) database, we identified all adult patients admitted primarily for gastric cancer from 2016 to 2019. We analyzed demographic characteristics of young adults (defined as those aged between 20 and 49-years-old) and older patients (aged 50 and above) as well as differences in in-hospital mortality, total hospital charges, and length of stay. Multivariate logistic regression analysis was conducted to adjust for confounders. Results: During the period studied, 77,720 patients were admitted with gastric cancer, of which 9,650 (12.4%) were young adults and 68,115 (87.6%) were old individuals. Young adults were more likely to be female (42.4 vs. 35.6%, p &lt; 0.01). Hispanics comprised 30.9% of admissions for gastric cancer of young adults (vs. 15% in older adults p-value &lt;0.01). Young adults were also over 3 times more likely to be uninsured than older individuals (9.6 vs. 2.6%, p-value &lt;0.01) and more likely to be cared for in urban (98.2 vs. 96.2%, p &lt; 0.01) and teaching (85.4 vs. 80.8%, p &lt; 0.01) hospitals. Young adults had longer lengths of stay and lower hospital charges (see table). No difference was found in mortality, despite a lower comorbidity burden in young adults based on the Charlson Comorbidity Index, possibly due to young adults being candidates for more aggressive therapy and having more aggressive disease. Conclusions: The higher incidence of gastric cancer in Hispanic and uninsured young adults poses a complex public health issue, especially in the context of recent research suggesting more aggressive disease in this population. The reported findings likely reflect both a shift in the U.S. population over the years as well as a rising incidence among Hispanic young adults. It is important to increase awareness of these epidemiological disparities. Further research is needed to determine whether establishing screening programs for gastric cancer in certain populations might be beneficial in the U.S. [Table: see text]

A multiplex DNA methylation assay for noninvasive early detection of gastric cancer.

300 Background: Gastric cancer (GC) is the fifth leading cancer that ranked fourth in cancer mortality worldwide. Early screening and detection can significantly improve patients’ prognosis and survival. Although in standard GC diagnosis, gastroscopy provides sufficient diagnostic power for identifying GC in early stages, the invasive and costly procedure is not suitable for screening and has low compliance in countries with high GC incidence and large populations. Furthermore, the serum-based GC related biomarkers and non-invasive tests (serum pepsinogen I and II, gastrin-17, and anti-Helicobacter pylori IgG antibody tests) showed insufficient evidence as cost-effective GC screening approaches. A non-invasive DNA methylation assay with high sensitivity was aimed to develop and validate as a potential alternative for GC early detection. Methods: A multiplex quantitative PCR (qPCR) assay for detecting GC-specific DNA methylation markers in plasma was developed, in which the markers were further optimized from a reported seven-marker panel based on a pilot case-control study with 63 GC and 130 non-GC samples. The GC detection model of the assay was developed and locked down in the first cohort consisting of 54 GC and 79 non-GC samples. The second validation cohort with 117 GC and 309 non-GC samples was used to evaluate the assay performance. All plasma samples used in the two cohorts were prospectively collected from patients diagnosed with GC or other gastrointestinal diseases or from healthy donors. Results: The multiplex DNA methylation assay showed an overall sensitivity and specificity of 80% (95% CI: 77–83%) and 65% (95% CI: 63–66%) in the model development cohort, respectively, with a sensitivity of 80% (95% CI: 65–95%, n=10) in the detection of stage I GC. The assay revealed similar performance characteristics in the validation cohort, with an overall sensitivity of 82% (95% CI: 80–83%), a specificity of 69% (95% CI: 68–69%), and a sensitivity of 78% (95% CI: 74–82%, n=41) for the stage I GC detection. The DNA methylation assay outperformed the reported serum-based GC related biomarkers and non-invasive tests (sensitivity of 69.6-70.7% and specificity of 66.8-67.8%) with higher sensitivity, particularly in the stage I GC with a comparable specificity. Conclusions: The multiplex DNA methylation assay provides a potential cost-effective tool that features high sensitivity for GC early detection.

Phylogenetic origin of Helicobacter pylori pathogenicity island and risk of stomach cancer and high-grade premalignant gastric lesions.

Infection by Helicobacter pylori (Hp) has been causally linked to risk of gastric cancer (GC). The coevolution of Hp and humans shaped the risk of GC as our species left Africa and migrated to the other continents. Latin America (LatAm) is a high GC incidence region where Hp evolved uniquely in the 500 years since European colonization. Differential virulence of the Hp cagA -pathogenicity island (cagPAI) by ancestral origin has been reported. We hypothesized that Hp phylogenetic origin might play a role in determining GC risk in LatAm. We used genotypes of 50 Hp genetic variants mapping to the Hp cagPAI, studied in 1220 subjects from Venezuela, Colombia, Mexico and Paraguay, who were infected with cagA-positive Hp, including 150 GC, 177 high-grade premalignant lesions (HGPMLs) and 893 low-grade premalignant lesions. We estimated the phylogenetic origin of Hp cagPAI in all study subjects by use of the STRUCTURE software and principal component analysis (PCA) and tested whether the estimated African ancestry percentage was associated with the risk of GC or HGPML. African ancestral component estimates by STRUCTURE and PCA were highly correlated. STRUCTURE-based African origin estimate was not significantly associated with the risk of HGPML, but it was inversely associated with GC risk: the OR associated with the continuous values of African component was 0.09 (95% CI, 0.01-0.85; P = 0.035). Similar trends were observed for GC with PCA-based estimates, but the association was not statistically significant. These results suggest that Hp ancestral origin may play a role in gastric carcinogenesis.

Cost-Effectiveness Analysis of Hp and New Gastric Cancer Screening Scoring System for Screening and Prevention of Gastric Cancer.

Gastric cancer is one of the most common gastrointestinal cancers. Early diagnosis can improve the 5-year survival rate. This study aimed to evaluate the cost-effectiveness of Helicobacter pylori (Hp) and a new gastric cancer screening scoring system (NGCS) in areas with a high incidence of gastric cancer. A decision-analytic Markov model was constructed based on the theory and method of cost-effectiveness analysis, which included three decisions: no screening, Hp screening, and NGCS screening. The uncertainty of each parameter in the model was determined using a one-way sensitivity analysis and probability sensitivity analysis. The results of the cost-effectiveness analysis revealed that the application of the NGCS had the highest cost-effectiveness, while the one-way sensitivity analysis revealed that the probability of intestinal metaplasia progression to dysplasia had the most significant effect on the incremental cost-effectiveness ratio. The probability sensitivity analysis concluded that the result of the NGCS having the highest cost-effectiveness was stable. Although the application of the NGCS will require upfront screening costs, it can significantly improve the detection rate of early gastric cancer and save the consequent long-term healthcare costs. It is practicable and can be popularized in China.

Descriptive Study of Tumor Immune Microenvironment and Epstein-Barr Virus Infection in Gastric Adenocarcinoma

Introduction. The Cauca region, in Colombia, has a high incidence of gastric cancer and there are few studies describing tumor microenvironment in gastric cancer samples obtained from this geographic region. Aim. The aim of this study was to describe the infiltration of CD3+, CD8+ T cells, the expression of programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1), and Epstein-Barr virus infection in biopsies from Cauca patients with advanced intestinal-type gastric adenocarcinoma. Methodology. This is a descriptive cross-sectional study of 24 gastrectomy samples out of 48 samples analyzed. Expression of CD3, CD8, PD-1, and PD-L1 was analyzed using immunohistochemistry, and infection by Epstein-Barr virus was analyzed by Epstein-Barr virus-encoded small RNA in-situ hybridization (EBER-ISH) in gastric tissue samples on formalin-fixed, paraffin-embedded. Finally, the immunoscore and the Combined Positive Score were calculated. Results. ITGA samples were 21.8% ± 13.6% and 14.8% ± 14.8% CD3 + and CD8 + positive respectively, 100% had low PD-1 expression, CPS score for PDL-1, 91.7% had &lt;1 and 8.3% had &gt;1. In EBER-ISH, 20.8% were positive, and in immunoscore, 16.7% had a score &gt; 25%. Conclusion. This paper reports advanced ITGA cases with an atypical tumor microenvironment, compared to previously reported data. It is important to consider that the tumor microenvironment in gastric cancer is heterogeneous, which makes the analysis of microsatellite instability in this type of sample relevant.

The management of Helicobacter pylori infection and prevention and control of gastric cancer in China.

Helicobacter pylori (H. pylori) infection, a type-1 carcinogen, was closely associated with gastric cancer (GC). Successfully eradicating H. pylori infection could reduce the incidence of GC. China was a country with high incidence of GC and high prevalence of H. pylori infection. Nearly half of worldwide GC new cases and deaths attributed to H. pylori infection occurred in China. H. pylori prevalence varied over time with the improvement of socioeconomic status and sanitary conditions. The knowledge of antibiotic resistance rate in time was important to guide the clinical choice of antibiotics use in the regimens. With the publication of five Chinese consensus reports on the management of H. pylori infection and the effort of public preach of H. pylori-related knowledge, the standardization of H. pylori diagnosis and treatment by clinicians was improved. Bismuth-containing quadruple therapy was widely applied in clinical practice of H. pylori eradication because of high efficacy and safety. High-dose Proton Pump Inhibitor-amoxicillin dual therapy or vonoprazan-amoxicillin dual therapy showed comparable efficacy and lower side effects than bismuth-containing quadruple therapy, which were the alternative choice. The diagnosis rate of early GC was low and distinguishing Chinese GC risk population for the further endoscopy screening was important. Efforts have been done to establish prediction models to stratify GC risk in the Chinese GC risk population. We reviewed the current situation of the management of H. pylori infection and prevention and control of GC in China here.