Gastric Cancer In High-risk Population Research Articles

Initial screening of gastric cancer using oral contrast-enhanced trans-abdominal ultrasonography in rural asymptomatic individuals

Background & aimsInitial screening for high-risk population of gastric cancer (GC) is needed in rural areas of large-population countries. This study aims to explore the feasibility of applying noninvasive ultrasonography as an initial screening strategy to improve the early diagnosis and prevention of GC. MethodsOral contrast-enhanced trans-abdominal ultrasonography (OCTU) was initially applied to screen around 15,000 residents from 24 different rural villages of Changxing Island in Shanghai, China, facilitating the identification of high-risk population for further endoscopy examination. Results176 subjects (1.18 %) were initially identified with gastric diseases using OCTU while 14,787 ones (98.93 %) were normal with negative results. 145 out of 176 individuals (82.39 %) took further endoscopy examination, and 16 were diagnosed with GC with biopsy examination, with 9 of them at the early stage. We followed up with the Center for Disease Control and Prevention, and identified another 6 GC cases occurred within one year among OCTU-negative population, serving as an adjustment factor for sensitivity analysis. As a result, with a total of 22 GC cases included in this cohort, the positive predictive rate, the negative predictive value, sensitivity, and specificity were 9.09％, 99.96 %, 75.5 %, and 98.93 %, respectively. ConclusionsOCTU is feasible, non-invasive, low-cost, and widely acceptable in rural area, thus we proposed that OCTU is practicable to serve as a supplementary screening method to improve the early detection of GC in rural area of China and other developing countries with large population.

Effect of Helicobacter pylori Eradication on Gastric Cancer Prevention: Updated Report From a Randomized Controlled Trial With 26.5 Years of Follow-up

Helicobacter pylori infection is considered as the most important risk factor in the pathogenesis of gastric cancer. This study aims to evaluate the long-term effects of H pylori eradication treatment on the incidence and mortality of gastric cancer among a high-risk population. This prospective, randomized, placebo-controlled trial was conducted in a high-risk area in southern China in July 1994. A total of 1630 asymptomatic, H pylori-infected individuals were randomly assigned to receive standard triple therapy for H pylori eradication (n= 817) or placebo (n= 813), and were followed up until December 2020. The primary outcome was incidence of gastric cancer. Total and cause-specific mortalities were the secondary outcomes. During 26.5 years of follow-up, 21 participants (2.57%) in the treatment arm and 35 (4.31%) in the placebo arm were diagnosed with gastric cancer. Participants receiving H pylori treatment had a lower incidence of gastric cancer compared with their placebo counterparts (hazard ratio [HR], 0.57; 95% CI, 0.33-0.98). More obvious risk reduction was observed among those without premalignant gastric lesions (HR, 0.37; 95% CI, 0.15-0.95) and those without dyspepsia symptoms at baseline (HR, 0.44; 95% CI, 0.21-0.94). Furthermore, compared with 32 cases of gastric cancer observed among 527 participants with persistent H pylori infection in the placebo group, only 16 were identified in 625 subjects with successful eradication in the treatment group (HR, 0.46; 95% CI, 0.26-0.83). However, there were no statistically significant differences for any mortality end points between the 2 groups. Eradication of H pylori might confer a long-term protection against gastric cancer in high-risk populations, especially for infected individuals without precancerous gastric lesions at baseline.

S1425 A Community-Based Screening Survey for Gastric Cancer in High-Risk Populations

S1425 A Community-Based Screening Survey for Gastric Cancer in High-Risk Populations

Establish a Scoring Model for High-Risk Population of Gastric Cancer and Study on the Pattern of Opportunistic Screening.

Objective To investigate and study the related risk factors of gastric cancer (GC) patients, to establish a high-risk scoring model of GC by multiple logistic regression analysis, and to explore the establishment of a GC screening mode with clinical opportunistic screening as the main method, and by using the pattern of opportunistic screening to establish the screening of high-risk GC patients and the choice of screening methods in the clinical outpatient work. Methods Collected the epidemiological questionnaire of 99 GC cases and 284 non-GC patients (other chronic gastric diseases and normal) diagnosed by the General Hospital of Ningxia Medical University from October 2017 to March 2019. Serum pepsinogen (PG) levels were measured by enzyme-linked immunosorbent assay (ELISA) and confirmed Helicobacter pylori (Hp) infection in gastric mucosa tissues by Giemsa staining. Determined the high-risk factors and established a scoring model through unconditional logistic regression model analysis, and the ROC curve determined the cut-off value. Then, we followed up 26 patients of nongastric cancer patients constituted a validation group, which validated the model. Results The high-risk factors of GC included age ≥ 55, male, drinking cellar or well water, family history of GC, Hp infection, PGI ≤ 43.6 μg/L, and PGI/PGII ≤ 2.1. Established the high-risk model: Y = A × age + 30 × gender + 30 × drinking water + 30 × Hp infection + 50 × family history of GC + B × PG level. The ROC curve determined that the cut-off value for high-risk GC population was ≥155, and the area under the curve (AUC) was 0.875, the sensitivity and specificity were 87.9% and 71.5%. Conclusions According to the risk factors of GC, using statistical methods can establish a high-risk scoring model of GC, and the score ≥ 155 is divided into the screening cut-off value for high-risk GC population. Using this model for clinical outpatient GC screening is cost-effective and has high sensitivity and specificity.

Association Between Lifestyle Factors, Vitamin and Garlic Supplementation, and Gastric Cancer Outcomes

The associations of lifestyle factors with gastric cancer (GC) are still underexplored in populations in China. Long-term nutritional supplementation may prevent GC in high-risk populations, but the possible effect modification by lifestyle factors remains unknown. To evaluate how lifestyle factors, including smoking, alcohol intake, and diet, may change the risk of GC incidence and mortality and whether the effects of vitamin and garlic supplementation on GC are associated with major lifestyle factors. This is a secondary analysis of the Shandong Intervention Trial, a masked, randomized, placebo-controlled trial that aimed to assess the effect of vitamin and garlic supplementations and Helicobacter pylori treatment on GC in a factorial design with 22.3 years of follow-up. The study took place in Linqu County, Shandong province, China, a high-risk area for GC. Data were collected from Jully 1995 to December 2017. Overall, 3365 participants aged 35 to 64 years identified in 13 randomly selected villages who agreed to undergo gastroscopy were invited to participate in the trial and were included in the analysis. Data analysis was conducted from March to May 2019. Participants received vitamin and garlic supplementation for 7.3 years, H pylori treatment for 2 weeks (among participants with H pylori ), or placebo. The primary outcomes were GC incidence and GC mortality (1995-2017). We also examined the progression of gastric lesions (1995-2003) as a secondary outcome. Of the 3365 participants (mean [SD] age, 47.1 [9.2] years; 1639 [48.7%] women), 1677 (49.8%) were randomized to receive active vitamin supplementation, with 1688 (50.2%) receiving placebo, and 1678 (49.9%) receiving active garlic supplementation, with 1687 (50.1%) receiving placebo. Overall, 151 GC cases (4.5%) and 94 GC deaths (2.8%) were identified. Smoking was associated with increased risk of GC incidence (odds ratio, 1.72; 95% CI, 1.003-2.93) and mortality (hazard ratio [HR], 2.01; 95% CI, 1.01-3.98). Smoking was not associated with changes to the effects of vitamin or garlic supplementation. The protective effect on GC mortality associated with garlic supplementation was observed only among those not drinking alcohol (never drank alcohol: HR, 0.33; 95% CI, 0.15-0.75; ever drank alcohol: HR, 0.92; 95% CI, 0.55-1.54; P for interaction = .03), and significant interactions were only seen among participants with H pylori (never drank alcohol: HR, 0.31; 95% CI, 0.12-0.78; ever drank alcohol: HR, 0.91; 95% CI, 0.52-1.60; P for interaction = .04). No significant interactions between vitamin supplementation and lifestyle factors were found. In this secondary analysis of a randomized clinical trial, smoking was associated with an increased risk of GC incidence and mortality. Not drinking alcohol was associated with a stronger beneficial effect of garlic supplementation on GC prevention. Our findings provide new insights into lifestyle intervention for GC prevention, suggesting that mass GC prevention strategies may need to be tailored to specific population subgroups to maximize the potential beneficial effect. ClinicalTrials.gov Identifier: NCT00339768.

Methylation and Expression of Nonclustered Protocadherins Encoding Genes and Risk of Precancerous Gastric Lesions in a High-Risk Population.

Nonclustered protocadherins (PCDH) family is a group of cell-cell adhesion molecules. We have found differentially methylated genes in the nonclustered PCDHs family associated with Helicobacter pylori (H. pylori) infection in prior genome-wide methylation analysis. To further investigate the methylation and expression of nonclustered PCDHs encoding genes in H. pylori--related gastric carcinogenesis process, four candidate genes including PCDH7, PCDH10, PCDH17, and PCDH20 were selected, which were reported to be tumor suppressors for digestive cancers. A total of 747 participants with a spectrum of gastric lesions were enrolled from a high-risk population of gastric cancer. Promoter methylation levels of four genes were significantly higher in H. pylori-positive subjects than the negative group (all P < 0.001). Elevated methylation levels of PCDH10 and PCDH17 were observed with the increasing severity of gastric lesions (both P trend < 0.001). In the protein expression analysis, PCDH17 expression was inversely associated with gastric lesions; the OR [95% confidence interval (CI)] was 0.49 (0.26-0.95) for chronic atrophic gastritis (CAG), 0.31 (0.15-0.63) for intestinal metaplasia, and 0.38 (0.19-0.75) for indefinite dysplasia and dysplasia, compared with superficial gastritis. In addition, PCDH10 expression was significantly lower in CAG (OR, 0.40; 95% CI, 0.24-0.68). The inverse association between methylation and protein expression of PCDH10 and PCDH17 was further supported when we explored the methylation and mRNA expression in The Cancer Genome Atlas database (all P < 0.001). Our study found elevated promoter methylation and decreased expression of PCDH10 and PCDH17 in advanced gastric lesions, suggesting that elevated PCDH10 and PCDH17 methylation may be an early event in gastric carcinogenesis. Cancer Prev Res; 11(11); 717-26. ©2018 AACR.

The Relationship between Helicobacter Pylori Virulence Factors and Gastric Carcinoma

Background: Helicobacter pylori is a gram-negative microaerophilic bacterium found usually in the stomach and use several mechanisms to survive in the stomach lumen. The presence of these bacteria in the stomach can lead to gastritis and reduction in stomach acid production. Aim of the work: this study aimed to investigate the seroprevalence of six highly immunogenic virulence factors (Cag A, Vac A, Gro EL, gGT, Hcp C and Ure A) in patients with different gastric histology in a high-risk population of gastric cancer and explore the relationship between H. pylori virulence factors and gastric carcinoma. Methods: this study included 100 patients: 25 patients were diagnosed histopathologically as gastric cancer (Group I) and 75 patients were diagnosed endoscopically as mild gastritis (Group II). Their samples were collected from Military Armed Hospitals. Noninvasive serologic test was performed to detect immune responses to H. pylori by stool antigen test, ELISA and by Recomoline H. pylori test. Results: on comparing results of gastric carcinoma and chronic gastritis by Recomoline H. pylori test, it was found that Cag A was detected in 88% (22/25) in group I. While, in group II it was 57.33% (43/75) of cases and Vac A was detected in 80% (20/25) in group I while, it was in group II in 44% (33/75) of cases. Gro EL was detected in 72% (18/25) in group I while; it was 49.33% (37/75) group II and Urea A was 52% (13/25) in group I while, it was 52% (39/75) in group II. Hcp c was 56% (14/25) in group I while, it was 40% (30/75) in group II and gGT was 48% (12/25) in group I while, it was 34.67% (26/75) in group II. Conclusion: in this study, a statistically significant association was found between Cag A, Vac A and Gro EL antigen in the studied groups of patients. However, no such statistically significant association was found between Urea A, Hcp c and gGT antigen. (P value > 0.05). Thus, Cag A, Vac A and Gro EL antigen proved to be virulence markers for gastric carcinoma group.

Genomic variability of Helicobacter pylori isolates of gastric regions from two Colombian populations.

AIMTo compare the genomic variability and the multiple colonization of Helicobacter pylori (H. pylori) in patients with chronic gastritis from two Colombian populations with contrast in the risk of developing gastric cancer (GC): Túquerres-Nariño (High risk) and Tumaco-Nariño (Low risk).METHODSFour hundred and nine patients from both genders with dyspeptic symptoms were studied. Seventy-two patients were included in whom H. pylori was isolated from three anatomic regions of the gastric mucosa, (31/206) of the high risk population of GC (Túquerres) and (41/203) of the low risk population of GC (Tumaco). The isolates were genotyped by PCR-RAPD. Genetic diversity between the isolates was evaluated by conglomerates analysis and multiple correspondence analyses.RESULTSThe proportion of virulent genotypes of H. pylori was 99% in Túquerres and 94% in Tumaco. The coefficient of similarity of Nei-Li showed greater genetic diversity among isolates of Túquerres (0.13) than those of Tumaco (0.07). After adjusting by age, gender and type of gastritis, the multiple colonization was 1.7 times more frequent in Túquerres than in Tumaco (P = 0.05).CONCLUSIONIn Túquerres, high risk of GC there was a greater probability of multiple colonization by H. pylori. From the analysis of the results of the PCR-RAPD, it was found higher genetic variability in the isolates of H. pylori in the population of high risk for the development of GC.

Quadruple therapy versus standard triple therapy for eradication of Helicobacter pylori in Kuwait

Background and study aimsChronic infection caused by Helicobacter pylori (H. pylori) is associated with chronic gastritis, peptic ulcer disease, and gastric cancer. Eradication of H. pylori reduces morbidity of chronic gastritis and incidence of gastric cancer in high-risk population. We aimed at testing the efficacy of clarithromycin-based triple therapy and bismuth-based quadruple therapy for eradicating H. pylori in patients with chronic gastritis in Kuwait. Patients and methodsA total of 218 dyspeptic patients from different countries who were proved to have chronic gastritis by endoscopy and gastric biopsy were enroled. All of them were naïve to H. pylori eradication therapy. They were randomised into two groups: group A, received triple therapy (omeprazole, amoxicillin, and clarithromycin) for 10days; and group B, received quadruple therapy (omeprazole, bismuth subcitrate potassium, tetracycline, and metronidazole) for 10days. All patients were tested for eradication of H. pylori by carbon-13 urea breath test 4weeks after treatment. ResultsTotal response rate of eradication therapy in both groups was 77.5% (n=169). However, group B (n=100) had a higher eradication rate (88%) than group A (n=118) (68.6%). H. pylori eradication rate was significantly higher in males (84.2%) than females (70.2%) in both groups (p<0.01). There were no differences in eradication rates with regard to median age or nationality. ConclusionBismuth-based quadruple therapy is more effective as a first-line therapy than clarithromycin-based triple therapy for eradicating H. pylori in patients with H. pylori-related chronic gastritis in Kuwait.

How to improve the diagnosis rate of early gastric cancer in China

China has great burden of gastric cancer, and the diagnosis rate of early gastric cancer is relatively low (<10%). To perform screening, early endoscopic diagnosis and treatment of gastric cancer in high-risk population is a feasible and efficient way to change the current status. Therefore, the Chinese Society of Digestive Endoscopy recently issued Consensus on screening, "Endoscopic diagnosis and treatment of early gastric cancer screening in China". The consensus suggests a feasible and efficient strategy for early detection of gastric cancer: screening with non-invasive procedures, followed by intensive endoscopic examination for screened high-risk population. In this article, we also describe the current status, the causes, high-risk population and early diagnosis of gastric cancer in China; and review the new development of serology and endoscopic techniques for early diagnosis.

Coffee Intake and Gastric Cancer Risk: The Singapore Chinese Health Study

Despite experimental evidence showing chemopreventive effects of coffee-related compounds on gastric carcinogenesis, epidemiologic studies generally do not support coffee-gastric cancer associations. Observational data are lacking among high-risk populations with sufficient regular coffee consumption. We examined the association between caffeinated coffee intake and gastric cancer risk in a population-based cohort that enrolled 63,257 Chinese men and women ages 45 to 74 years between 1993 and 1998 in Singapore. Incident gastric cancer cases (n = 647) were identified after a mean follow-up of 14.7 years. Biomarkers of Helicobacter pylori (H. pylori) infection were measured in a subset of gastric cancer cases with blood collected before cancer diagnosis and their matched controls. In the total cohort, daily versus nondaily coffee intake was associated with a statistically nonsignificant decrease in gastric cancer risk [HR = 0.85; 95% confidence interval (CI), 0.69-1.04]. In women, the inverse association strengthened and reached statistical significance (HR = 0.63; 95% CI, 0.46-0.87). In analyses restricted to never smokers and nondrinkers of alcohol, inverse associations strengthened in the total cohort (HR = 0.69; 95% CI, 0.52-0.91) and in women (HR = 0.52; 95% CI, 0.37-0.74). There was no coffee-gastric cancer risk association among men, regardless of smoking status or alcohol consumption. Similar results were observed in the nested case-control study after adjustment for H. pylori infection. Daily coffee consumption may reduce the risk of gastric cancer in high-risk populations, especially among women. Research aimed at identifying the compounds in coffee that may protect against gastric carcinogenesis is warranted.

Serological assessment of Helicobacter pylori-specific antibodies and their association with gastric lesions in a high-risk population

To determine the distributions of six Helicobacter pylori (Hp)-specific antibodies in a high-risk population of gastric cancer (GC) and explore the relationship between Hp virulence factors and precancerous gastric lesions. Based on the two intervention trials conducted in Linqu County, the seropositivities for CagA, VacA, GroEL, UreA, HcpC and GGT were assessed by recombinant immunoassay (recomLine) in 623 participants with H. pylori infection determined by (13)C-urea breath test ((13)C-UBT) and/or enzyme linked immunosorbent assay (ELISA). In a total of 623 participants were detected by recomLine analysis, of which 594 were Hp-positive. The seropositivities rates of CagA, VacA, GroEL, UreA, HcpC and GGT were 84.0%, 38.2%, 66.7%, 17.7%, 58.8% and 42.8%, respectively. A total of 523 participants were determined as type I infection of Hp, accounting for 88.1%. Compared with superficial gastritis (SG), the infection rate of Hp type I was higher in the chronic atrophic gastritis (CAG) (P = 0.001). The results of this population-based study suggest that the virulence factors of Hp may be related to the development of GC in a Chinese high-risk population. The recomLine analysis may serve as a tool for identification of Hp strains and prediction of high-risk population of GC.

Genetic polymorphism of PSCA and risk of advanced precancerous gastric lesions in a Chinese population

Objective: To evaluate the relationship between the genetic polymorphism of prostate stem cell antigen (PSCA) and the risk of advanced precancerous gastric lesions including intestinal metaplasia(IM) and dysplasia(Dys), a population-based study was conducted in Linqu County, a high-risk area of gastric cancer (GC) in China. Methods: The prevalence of gastric lesions including superficial gastritis(SG), chronic atrophic gastritis(CAG), IM and Dys was determined by histopathologic examination. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The effects of PSCA genetic variant on the risks of IM and Dys were calculated by unconditional logistic regression. Results: Multivariate analysis revealed subjects carrying PSCA rs2294008 CT/TT genotype were associated with an increased risk of IM (OR=1.38, 95% CI=1.11-1.71) and Dys (OR=1.75, 95% CI=1.36-2.26), especially for subjects with H.pylori infection (IM: OR=1.34, 95% CI=1.05-1.71; Dys: OR=1.82, 95% CI=1.37-2.42). Furthermore, H. pylori infection and PSCA rs2294008 CT/TT genotype were observed to jointly elevate the risk of IM (OR=3.32, 95% CI=2.33-4.71) and Dys (OR=4.58, 95% CI=2.99-7.04). Conclusion: This study suggested that PSCA rs2294008 might have an impact on the risk of IM or Dys among the high risk population of GC.

Adjuvant treatment of gastric cancer in a long term follow-up

BACKGROUND: Advanced gastric cancer carries a poor-prognosis. The best extent of the node dissection and the value of postoperative adjuvant treatments remain open questions. AIM: To study the efficacy of adjuvant chemoradiation and the prognostic value of some clinico-pathological variables in gastric cancer previously submitted to surgery. METHODS: Retrospective single institution study of 69 patients with histological diagnoses of gastric adenocarcinoma, consecutively submitted to radical surgery with curative intent in a five years period. Lymph node dissection was either D1 or D2 at the surgeon's description. All patients were submitted to adjuvant chemoradiation according to MacDonald et al.². Treatment discontinuation and early deaths were considered as serious toxic events. Clinical-pathological variables (the extent D level of the node dissection, T/N-stage, histological subtype, margin status, number of the dissected nodes) were correlated to the results. Overall survival was estimated according to the Kaplan-Meier method and the curves were compared by the log-rank test. RESULTS: Patients characteristics: 48 male/21 female, median age 56,4 y (30-79). In 25 patients, the extent of node dissection was D1, in 41 was D2 and D0 in 3. Staging (n): T2 (16); T3 (49); T4 (4); No (11); N1 (29); N2 (20); N3 (8); Nx (1). Histological subtype: intestinal (45), diffuse (19) and unknown (5). Margins were free in 57 patients, the median number of dissected nodes was 31 (0-120). They were treated with linear acelerator 6 MV photons, AP/PA fields with 45Gy in 5 weeks in 90% of the patients and the treatment was done in a mean time of 19,2 weeks. In the median follow-up of 19,3mo (8-52,5mo), 52 patients with more than 24 months of follow-up occurred 38 deaths. The median overall survival for all patients was 22,2 months. Seven (10%) patients presented serious toxic events and treatment was discontinued. Six (8,6%) refused to continue the treatment. The acute toxicity was predominantly gastrointestinal (63), neurological (2), hematological (3), stroke (1). Toxicity was considered GI/GII (52), GIII (10) and GIV (1). Recurrences were local (6); loco-regional (2); local and distant (5); regional (9); regional and distant (2) and only distant (4). There were two patients with progression of the disease and 11 were lost of the follow-up (16%). Twenty eight (40,5%) were alive without disease. In the 52 patients with longer follow-up the Kaplan Mayer analysis showed: better overall survival was observed in those patients presenting T2 versus T3/T4 tumors (not reached vs 17,3 mo, HR 0,35, 95%CI , P=0,03), N0N1 vs N2/N3 tumors (32,7 mo vs 14,5 mo, P=0,0041) and free vs compromised surgical margins (25,7 vs 17,2 mo, P=0,03). No difference in either T (P=0,430, Fisher exact test), N-stage (P= 0,077), or overall survival (27,1 mo vs 17,3 mo, P=0,28) were detected between patients submitted to D1 or D2 dissections. CONCLUSIONS: In this high-risk population of gastric cancer submitted to adjuvant chemoradiation, D2 dissection was not superior to D1 when chemoradiation was administered, in spite of the retrospective nature of these data and the low number of studied patients. Patients with compromised surgical margins have a very poor prognosis and the addition of chemoradiation seems not improve the survival of these patients.

Abstract PL02-01: Global trends in cancer incidence: priorities for prevention

Abstract PL02-01: Global trends in cancer incidence: priorities for prevention