Type Ⅰ and type Ⅱ Helicobacter pylori infection status and their impact on gastrin and pepsinogen level in a gastric cancer prevalent area

BACKGROUND Type I Helicobacter pylori(H.pylori)infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis.However,its infection status in stepwise gastric disease progression in this gastric cancer prevalent area has not been evaluated;it is also not known its impact on commonly used epidemiological gastric cancer risk markers such as gastrin-17(G-17)and pepsinogens(PGs)during clinical practice.AIM To explore the prevalence of type I and type II H.pylori infection status and their impact on G-17 and PG levels in clinical practice.METHODS Thirty-five hundred and seventy-two hospital admitted patients with upper gastrointestinal symptoms were examined,and 523 patients were enrolled in this study.H.pylori infection was confirmed by both 13C-urea breath test and serological assay.Patients were divided into non-atrophic gastritis(NAG),nonatrophic gastritis with erosion(NAGE),chronic atrophic gastritis(CAG),peptic ulcers(PU)and gastric cancer(GC)groups.Their serological G-17,PG I and PG II values and PG I/PG II ratio were also measured.RESULTS A total H.pylori infection rate of 3572 examined patients was 75.9%,the infection rate of 523 enrolled patients was 76.9%,among which type I H.pylori infection accounted for 72.4%(291/402)and type II was 27.6%;88.4%of GC patients were H.pylori positive,and 84.2%of them were type I infection,only 11.6%of GC patients were H.pylori negative.Infection rates of type I H.pylori in NAG,NAGE,CAG,PU and GC groups were 67.9%,62.7%,79.7%,77.6%and 84.2%,respectively.H.pylori infection resulted in significantly higher G-17 and PG II values and decreased PG I/PG II ratio.Both types of H.pylori induced higher G-17 level,but type I strain infection resulted in an increased PG II level and decreased PG I/PG II ratio in NAG,NAGE and CAG groups over uninfected controls.Overall PG I levels showed no difference among all disease groups and in the presence or absence of H.pylori;in stratified analysis,its level was increased in GC and PU patients in H.pylori and type I H.pylori-positive groups.CONCLUSION Type I H.pylori infection is the major form of infection in this geographic region,and a very low percentage(11.6%)of GC patients are not infected by H.pylori.Both types of H.pylori induce an increase in G-17 level,while type I H.pylori is the major strain that affects PG I and PG IIs level and PG I/PG II ratio in stepwise chronic gastric disease.The data provide insights into H.pylori infection status and indicate the necessity and urgency for bacteria eradication and disease prevention in clinical practice.

Value of serum pepsinogenⅠ andⅡ ratio for evaluating the malignant biological behaviors in gastric cancer lesions

Objective:To study the value of serum pepsinogenⅠ andⅡ ratio (PGR) for evaluating the malignant biological behaviors in gastric cancer lesions.Methods:The patients with gastric cancer who underwent radical surgery in 363 Hospital between July 2015 and February 2018 were selected as the gastric cancer group in the study, and the volunteers who had physical examination in 363 Hospital during the same period were selected as the control group. Serum was collected to measure pepsinogenⅠ and pepsinogenⅡ and then calculate the PGR;gastric cancer lesions were collected to measure the expression of oncogenes and angiogenesis genes.Results:Serum PGR level of the gastric cancer group was significantly lower than that of the control group, serum PGR level of the patients with moderately-highly differentiated gastric cancer was significantly higher than that of the patients with lowly differentiated gastric cancer, serum PGR level of the patients with TNM stage III gastric cancer was significantly lower than that of the patients with TNM stage I+II gastric cancer, and serum PGR level of the gastric cancer patients with lymph node metastasis was significantly lower than that of the gastric cancer patients without lymph node metastasis;PGR=3.8 was taken as the cutoff point, and p53 and TXNIP mRNA expression in the lesions of the gastric cancer patients with PGR < 3.8 were significantly lower than those of the gastric cancer patients with PGR > 3.8 while Bcl-2,β-catenin, Survivin, COX-2, HIF-1α, VEGF, c-Met and CNPY2 mRNA expression were significantly higher than those of the gastric cancer patients with PGR > 3.8.Conclusion:The decrease of PGR in serum of patients with gastric cancer is valuable for evaluating the pathological process and malignant biological behaviors.

Correlation of serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content with malignant proliferation of cancer cells in patients with gastric cancer

Objective: To investigate the correlation of serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content with malignant proliferation of cancer cells in patients with gastric cancer. Methods:Superficial gastritis group (n=247), gastric ulcer group (n=159) and gastric cancer group (n=97) who were pathologically diagnosed by gastroscopy in Chongqing wanzhou district people's hospital of 5 between August 2016 and August 2017 were selected, and the differences in serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content as well as proliferation and apoptosis gene expression in lesion tissue were compared among the three groups. Pearson test was used to evaluate the correlation of pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content with malignant proliferation activity of cancer cells in patients with gastric cancer. Results: Serum pepsinogenⅠ/Ⅱ ratio and gastrin-17 content in gastric cancer group were lower than those in gastric ulcer group and superficial gastritis group. Proliferation genes EIF5A2, MACF1 and PIK3CD mRNA expression levels in gastric cancer group were higher than those in gastric ulcer group and superficial gastritis group whereas SIRT1 mRNA expression level was lower than that in gastric ulcer group and superficial gastritis group;apoptosis gene Livin mRNA expression level was higher than that in gastric ulcer group and superficial gastritis group whereas Bad and Noxa mRNA expression levels were lower than those in gastric ulcer group and superficial gastritis group;serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content in gastric cancer group were negatively correlated with EIF5A2, MACF1, PIK3CD and Livin mRNA expression levels, and positively correlated with SIRT1, Bad and Noxa mRNA expression levels. Conclusion: The serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content abnormally reduce in patients with gastric cancer, and the specific levels are directly correlated with gastric cancer cell proliferation and apoptosis activity.

Efficacy and safety of endoscopic submucosal dissection for early gastric cancer and precancerous lesions in elderly patients

BACKGROUND With advancements in the development of endoscopic technologies,the endo-scopic submucosal dissection(ESD)has been one of the gold-standard therapies for early gastric cancer.AIM To investigate the efficacy and safety ESD in the treatment of early gastric cancer and precancerous lesions in the elderly patients.METHODS Seventy-eight elderly patients with early gastric cancer and precancerous lesions admitted to the Third Affiliated Hospital of Qiqihar Medical University were se-lected and classified into two groups according to the different surgical therapies they received between January 2021 and June 2022.Among them,39 patients treated with ESD were included in an experimental group,and 39 patients treated with endoscopic mucosal resection(EMR)were included in a control group.We compared the basic intraoperative conditions,postoperative short-term recovery,long-term recovery effects and functional status of gastric mucosa between the two groups;the basic intraoperative conditions included lesion resection,intra-operative bleeding and operation time;the postoperative short-term recovery assessment indexes were length of hospital stay and incidence of surgical complic-ations;and the long-term recovery assessment indexes were the recurrence rate at 1 year postoperatively and the survival situation at 1 year and 3 years postoper-atively;and we compared the preoperative and predischarge serum pepsinogen I(PG I)and PG II levels and PG I/PG II ratio in the two groups before surgery and discharge.RESULTS The curative resection rate and the rate of en bloc resection were higher in the experimental group than in the control group.The intraoperative bleeding volume was higher in the experimental group than in the control group.The operation time was longer in the experimental group than that in the control group,and the rate for base residual focus was lower in the experimental group than that of the control group,and the differences were all statistically significant(all P<0.05).The length of hospital stay was longer in the experi-mental group than in the control group,and the incidence of surgical complications,1-year postoperative recu-rrence rate and 3-year postoperative survival rate were lower in the experimental group than in the control group,and the differences were statistically significant(all P<0.05).However,the difference in the 1-year postoperative survival rate was not statistically significant between the two groups(P>0.05).Before discharge,PG I and PG I/PG II ratio were elevated in both groups compared with the preoperative period,and the above indexes were higher in the experimental group than those in the control group,and the differences were statistically significant(both P<0.05).Moreover,before discharge,PG II level was lower in both groups compared with the preoperative period,and the level was lower in the experimental group than in the control group,and the differences were all statistically significant(all P<0.05).CONCLUSION Compared with EMR,ESD surgery is more thorough.It reduces the rate of base residual focus,recurrence rate,surgical complications,and promotes the recovery of gastric cells and glandular function.It is safe and suitable for clinical application.

Dynamic expression of pepsinogen C in gastric cancer, precancerous lesions and Helicobacter pylori associated gastric diseases

AIM:To investigate the relationship between the expression of pepsinogen C (PGC) and gastric cancer, precancerous diseases, and Helicobacter pylori (H pylori) infection. METHODS: The expression of PGC was determined by immunohistochemistry method in 430 cases of gastric mucosa. H3 Pylori infection was determined by HE staining, PCR and ELISA in 318 specimens. RESULTS: The positive rate of PGC expression in 54 cases of normal gastric mucosa was 100%. The positive rates of PGC expression in superficial gastritis or gastric ulcer or erosion, atrophic gastritis or gastric dysplasia and gastric cancer decreased significantly in sequence (P<0.05; 100%/89.2% vs 14.3%/15.2% vs 2.4%). The over-expression rate of PGC in group of superficial gastritis with H pyloriinfection was higher than that in group without H pylori infection (P<0.05; x2= 0.032 28/33 vs 15/25). The positive rate of PGC expression in group of atrophic gastritis with H pylori infection was lower than that in group without H pylori infection (P<0.01; x2 = 0.003 4/61 vs9/30), and in dysplasia and gastric cancer. CONCLUSION: The level of PGC expression has a close relationship with the degree of malignancy of gastric mucosa and development of gastric lesions. There is a relationship between H pylori infection and expression of antigen PGC in gastric mucosa, the positive rate of PGC expression increases in early stage of gastric lesions with H pylori infection such as gastric inflammation and decreases during the late stage such as precancerous diseases and gastric cancer. PGC-negative cases with H py/ori-positive gastric lesions should be given special attention.

Serum pepsinogen Ⅱ is a better diagnostic marker in gastric cancer

AIM:To investigate screening makers for gastric cancer,we assessed the association between gastric cancer and serum pepsinogens(PGs).METHODS:The subjects comprised 450 patients with gastric cancer,111 individuals with gastric atrophy,and 961 healthy controls.Serum anti-Helicobacter pylori(H.pylori) immunoglobulin G(IgG),PGⅠand PG Ⅱ were detected by enzyme-linked immunosorbent assay.Gastric atrophy and gastric cancer were diagnosed by endoscopy and histopathological examinations.Odds ratios and 95%CIs were calculated using multivariate logistic regression.RESULTS:Rates of H.pylori infection remained high in Northeastern China.Rates of H.pylori IgG positivity were greater in the gastric cancer and gastric atrophy groups compared to the control group(69.1% and 75.7% vs 49.7%,P < 0.001).Higher levels of PG Ⅱ(15.9 μg/L and 13.9 μg/L vs 11.5 μg/L,P < 0.001) and lower PGⅠ/PG Ⅱ ratio(5.4 and 4.6 vs 8.4,P < 0.001) were found in patients with gastric cancer or gastric atrophy compared to healthy controls,whereas no correlation was found between the plasma PGⅠconcentration and risk of gastric cancer(P = 0.537).In addition,multivariate logistic analysis indicated that H.pylori infection and atrophic gastritis were independent risk factors for gastric cancer.Lower plasma PGⅠ/PG Ⅱ ratio was associated with higher risks of atrophy and gastric cancer.Furthermore,plasma PG Ⅱ?level?significantly?correlated?with?H.pyloriinfected gastric cancer.CONCLUSION:Serum PG Ⅱ concentration and PG Ⅰ/PG Ⅱ ratio are potential biomarkers for H.pyloriinfected gastric disease.PG Ⅱ is independently associated with risk of gastric cancer.

Roux-en-Y versus BillrothⅠreconstruction after distal gastrectomy for gastric cancer:A meta-analysis

AIM: To conduct a meta-analysis to compare Roux-en-Y (R-Y) gastrojejunostomy with gastroduodenal Billroth?I?(B-I) anastomosis after distal gastrectomy (DG) for gastric cancer.METHODS: A literature search was performed to identify studies comparing R-Y with B-I?after DG for gastric cancer from January 1990 to November 2012 in Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in The Cochrane Library. Pooled odds ratios (OR) or weighted mean differences (WMD) with 95%CI were calculated using either ?xed or random effects model. Operative outcomes such as operation time, intraoperative blood loss and postoperative outcomes such as anastomotic leakage and stricture, bile re?ux, remnant gastritis, re?ux esophagitis, dumping symptoms, delayed gastric emptying and hospital stay were the main outcomes assessed. Meta-analyses were performed using RevMan 5.0 software (Cochrane library).RESULTS: Four randomized controlled trials (RCTs) and 9 non-randomized observational clinical studies (OCS) involving 478 and 1402 patients respectively were included. Meta-analysis of RCTs revealed that R-Y reconstruction was associated with a reduced bile re?ux (OR 0.04, 95%CI: 0.01, 0.14; P < 0.00?001) and remnant gastritis (OR 0.43, 95%CI: 0.28, 0.66; P = 0.0001), however needing a longer operation time (WMD 40.02, 95%CI: 13.93, 66.11; P = 0.003). Meta-analysis of OCS also revealed R-Y reconstruction had a lower incidence of bile re?ux (OR 0.21, 95%CI: 0.08, 0.54; P = 0.001), remnant gastritis (OR 0.18, 95%CI: 0.11, 0.29; P < 0.00?001) and re?ux esophagitis (OR 0.48, 95%CI: 0.26, 0.89; P = 0.02). However, this reconstruction method was found to be associated with a longer operation time (WMD 31.30, 95%CI: 12.99, 49.60; P = 0.0008).CONCLUSION: This systematic review point towards some clinical advantages that are rendered by R-Y compared to B-I?reconstruction post DG. However there is a need for further adequately powered, well-designed RCTs comparing the same.

Effects of small interfering RNA inhibit Class Ⅰ phosphoinositide 3-kinase on human gastric cancer cells

AIM: To investigate the effects of small interfering RNA (siRNA)-mediated inhibition of Class?I?phosphoinositide 3-kinase (Class?I?PI3K) signal transduction on the proliferation, apoptosis, and autophagy of gastric cancer SGC7901 and MGC803 cells.METHODS: We constructed the recombinant replication adenovirus PI3K(I)-RNA interference (RNAi)-green fluorescent protein (GFP) and control adenovirus NC-RNAi-GFP, and infected it into human gastric cancer cells. MTT assay was used to determine the growth rate of the gastric cancer cells. Activation of autophagy was monitored with monodansylcadaverine (MDC) staining after adenovirus PI3K(I)-RNAi-GFP and control adenovirus NC-RNAi-GFP treatment. Immunofluorescence staining was used to detect the expression of microtubule-associated protein 1 light chain 3 (LC3). Mitochondrial membrane potential was measured using the fluorescent probe JC-1. The expression of autophagy was monitored with MDC, LC3 staining, and transmission electron microscopy. Western blotting was used to detect p53, Beclin-1, Bcl-2, and LC3 protein expression in the culture supernatant.RESULTS: The viability of gastric cancer cells was inhibited after siRNA targeting to the Class?I?PI3K blocked Class?I?PI3K signal pathway. MTT assays revealed that, after SGC7901 cancer cells were treated with adenovirus PI3K(I)-RNAi-GFP, the rate of inhibition reached 27.48% ± 2.71% at 24 h, 41.92% ± 2.02% at 48 h, and 50.85% ± 0.91% at 72 h. After MGC803 cancer cells were treated with adenovirus PI3K(I)-RNAi-GFP, the rate of inhibition reached 24.39% ± 0.93% at 24 h, 47.00% ± 0.87% at 48 h, and 70.30% ± 0.86% at 72 h (P < 0.05 compared to control group). It was determined that when 50 MOI, the transfection efficiency was 95% ± 2.4%. Adenovirus PI3K(I)-RNAi-GFP (50 MOI) induced mitochondrial dysfunction and activated cell apoptosis in SGC7901 cells, and the results described here prove that RNAi of Class?I?PI3K induced apoptosis in SGC7901 cells. The results showed that adenovirus PI3K(I)-RNAi-GFP transfection induced punctate distribution of LC3 immunoreactivity, indicating increased formation of autophagosomes. The results showed that the basal level of Beclin-1 and LC3 protein in SGC7901 cells was low. After incubating with adenovirus PI3K(I)-RNAi-GFP (50 MOI), Beclin-1, LC3, and p53 protein expression was significantly increased from 24 to 72 h. We also found that Bcl-2 protein expression down-regulated with the treatment of adenovirus PI3K(I)-RNAi-GFP (50 MOI). A number of isolated membranes, possibly derived from ribosome-free endoplasmic reticulum, were seen. These isolated membranes were elongated and curved to engulf a cytoplasmic fraction and organelles. We used transmission electron microscopy to identify ultrastructural changes in SGC7901 cells after adenovirus PI3K(I)-RNAi-GFP (50 MOI) treatment. Control cells showed a round shape and contained normal-looking organelles, nucleus, and chromatin, while adenovirus PI3K(I)-RNAi-GFP (50 MOI)-treated cells exhibited the typical signs of autophagy.CONCLUSION: After the Class?I?PI3K signaling pathway has been blocked by siRNA, the proliferation of cells was inhibited and the apoptosis of gastric cancer cells was enhanced.

Value of gastroscopy combined with serum pepsinogen in the diagnosis of high risk Hp related gastric cancer

Objective:To explore the value of Helicobacter pylori antibody (Hp-IgG) and serum pepsinogen (PG) combined with gastroscopy for screening early gastric cancer and precancerous lesions in high-risk groups, so as to provide references for early clinical prevention and diagnosis.Methods: A retrospective analysis of our hospital from December 2014 to December 2017 were elderly patients with gastric cancer 304 cases, selected admitted 122 cases of elderly patients with gastric precancerous lesion (divided into superficial gastritis group, 70 cases of chronic atrophic gastritis group 52 cases) and 156 cases to the hospital in healthy volunteers as the control group. The status and the positive rate of Helicobacter pylori 13C urea breath test and compared two groups of patients with infection;using enzyme-linked immunosorbent assay of serum pepsinogen I (PG I), II (PG II) and pepsin Hp-IgG quantitative and qualitative diagnosis of individual and combined diagnostic efficiency and the comparison of three kinds of index.Results: The four groups were compared, the serum PG level of I from high to low were superficial gastritis group, normal control group, atrophic gastritis group and gastric cancer group, the differences were statistically significant;serum PG II levels from high to low in gastric cancer group and superficial gastritis group. Atrophic gastritis group, normal control group, the differences were statistically significant. Compared with the three groups, the positive rate of Hp-IgG was 90.7% in the gastric cancer group, 45.6% in the superficial gastritis group, 52.5% in the atrophic gastritis group, and the gastric cancer group was higher than that in the precancerous lesion group, but there was no difference between the precancerous lesions group. In terms of diagnostic efficacy, the specificity and sensitivity of Helicobacter pylori combined with pepsinogen were higher than those of the single diagnosis. Conclusion: Hp-IgG and PG combined with gastroscopy in screening high-risk gastric cancer and its precancerous lesions are of high specificity, high sensitivity and can be popularized in clinic.

EXPRESSION OF PEPSINOGEN Ⅰ AND Ⅱ IN HUMAN GASTRIC CARCINOMA AND PRECARCINOUS LESION

The antibodies to Pgl and Pgll are used to do the immunohistochemical study In human gastric carcinoma and precarcinous lesion. The results show that in embryo gastric mucosa the expression of PgI is positive while Pgll Is negative: In normal gastric mucosa both Pgs are positive expression: In precarclnous lesion of stomach the positive rate of both Pgs decrease strikingly, and decrease further to the lowest level when the gastric cancer occurs. It is suggested that Pgl and Pgll are the special marker of normal gastric mucosa. There Is no obvious difference of Pgl and PgII In the various types of gastric carcinoma. Both Pgs levels in advanced gastric cancer are higher than that in early stage. Pgll expression is more In gastric cancer accompanied by lymphatic metastasis, which may be beneficial to the estimate of gastric carcinoma prognosis.

Clinical significance of combined determination of serum PGⅠ , PGⅡ and GAS for diagnosis of gastric cancer

To evaluate the clinical value of combined determination of serum PGⅠ, PGⅡ and GAS for early diag-nosis of gastric cancer, the serum levels of PGⅠ, PGⅡ and GAS in 190 healthy controls and 129 patients with gas-tric disorders were measured by RIA. The 129 patients include 68 cases of gastric cancer. The results showed that the serum levels of PGⅠ and PGⅠ/PGⅡ ratio in gastric cancer patients were obviously lower than those in healthy controls, while comparing with controls, the serum GAS levels were significantly higher. The diagnostic accuracy of the determinations for gastric cancer was evaluated by receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) levels of serum PGⅠ, PGⅠ/PGⅡ ratio and GAS were 0.833, 0.842 and 0.851, respec-tively. As serum PGⅠ or PGⅠ/PGⅡ ratio or GAS were combined, the sensitivity and specificity of determination for gastric cancer diagnosis were 94.2% and 73.4%, respectively. All these results indicated that the combined deter-mination of serum PGⅠ, PGⅡ and GAS levels may be used as a tool for primary screening of gastric cancer.

Diagnoses of gastric cancer and other gastric diseases by serum pepsinogen I and Ⅱ levels

１ＩｎｔｒｏｄｕｃｔｉｏｎＭａｎｙｒｅｃｅｎｔｆｏｒｅｉｇｎａｎｄｄｏｍｅｓｔｉｃｒｅｐｏｒｔｓｓｈｏｗｅｄｔｈｅｈｕｍａｎｓｅｒｕｍｐｅｐｓｉｎｏｇｅｎ（ＰＧ）ｌｅｖｅｌｓｗｅｒｅｖａｌｕａｂｌｅｉｎｔｈｅｄｉａｇｎｏｓｉｓｏｆｇａｓｔｒｉｃｄｉｓ...

皖南蝮蛇毒抑瘤组分-Ⅰ对胃癌MKN-28细胞增殖、迁移及凋亡的影响

目的:探讨皖南蝮蛇毒抑瘤组分-Ⅰ(agkistrodon halys venom antitumor componentⅠ,AHVAC-Ⅰ)对胃癌MKN-28细胞生物学行为的影响作用。方法:不同实验浓度(5、10和15μg/mL)AHAVC-Ⅰ处理胃癌细胞MKN-2824 h后,采用细胞增殖和毒性检测(cell counting kit-8,CCK-8)法检测细胞增殖活力;划痕实验和Tanswell小室检测细胞迁移能力;激光共聚焦显微镜(annexin VmCherry/DAPI双染)和流式细胞术(annexin VFITC/PI双染)检测细胞凋亡;Western blot检测细胞凋亡相关蛋白Caspease-3的表达水平。结果:AHVAC-Ⅰ各浓度组分别与正常对照组相比结果显示,随着AHVAC-Ⅰ浓度的增加,MKN-28细胞增殖活力逐渐下降(P<0.01),细胞迁移能力逐渐被抑制(P<0.01),细胞凋亡率增高(P<0.05),凋亡相关蛋白Caspease-3表达上调(P<0.01)。结论:AHVAC-Ⅰ抑制胃癌细胞MKN-28增殖和迁移,诱导其凋亡。

Screening for gastric cancer in China:Advances,challenges and visions

Gastric cancer(GC)is one of the major cancers in China and all over the world.Most GCs are diagnosed at an advanced stage with unfavorable prognosis.Along with some other countries,China has developed the government-funded national screening programs for GC and other major cancers.GC screening has been shown to effectively decrease the incidence of and mortality from GC in countries adopting nationwide screening programs(Japan and Korea)and in studies based on selected Chinese populations.The screening of GC relies mostly on gastroendoscopy,the accuracy,reliability and safety of which have been indicated by previous studies.However,considering its invasive screening approach,requirements on skilled endoscopists and pathologists,and a high cost,developing noninvasive methods to amend endoscopic screening would be highly needed.Numerous studies have examined biomarkers for GC screening and the combination of biomarkers involving pepsinogen,gastrin,and Helicobacter pylori antibodies has been proposed for risk stratification,seeking to narrow down the high-risk populations for further endoscopy.Despite all the achievements of endoscopic screening,evidence on appropriate screening age,intervals for repeated screening,novel biomarkers promoting precision prevention,and health economics need to be accumulated to inform policymakers on endoscopic screening in China.With the guide of Health China 2030 Planning Outline,we have golden opportunities to promote prevention and control of GC.In this review,we summarize the characteristics of screening programs in China and other East Asian countries and introduce the past and current approaches and strategies for GC screening,aiming for featuring the latest advances and key challenges,and illustrating future visions of GC screening.

A survey and evaluation of population-based screening for gastric cancer

Screening and early diagnosis of gastric cancer play important roles in reducing the mortality of gastric cancer. A vast amount of study data on gastric cancer screening and early diagnosis has been accumulated in and out of China in the past decades. The practice of gastric cancer screening has also been efficiently carried out in different countries and regions. However, no widely accepted principle of population screening for gastric cancer has been developed yet. Screening for gastric cancer requires extensive exploration both theoretically and practically. This article focuses on the method and program of gastric cancer screening based on population. Moreover, the current situation of gastric cancer screening and its evaluation are evaluated.

Current issues and future perspectives of gastric cancer screening

Gastric cancer remains the second leading cause of cancer death worldwide. About half of the incidence of gastric cancer is observed in East Asian countries, which show a higher mortality than other countries. The effectiveness of 3 new gastric cancer screening techniques, namely, upper gastrointestinal endoscopy, serological testing, and &#x0201c;screen and treat&#x0201d; method were extensively reviewed. Moreover, the phases of development for cancer screening were analyzed on the basis of the biomarker development road map. Several observational studies have reported the effectiveness of endoscopic screening in reducing mortality from gastric cancer. On the other hand, serologic testing has mainly been used for targeting the high-risk group for gastric cancer. To date, the effectiveness of new techniques for gastric cancer screening has remained limited. However, endoscopic screening is presently in the last trial phase of development before their introduction to population-based screening. To effectively introduce new techniques for gastric cancer screening in a community, incidence and mortality reduction from gastric cancer must be initially and thoroughly evaluated by conducting reliable studies. In addition to effectiveness evaluation, the balance of benefits and harms must be carefully assessed before introducing these new techniques for population-based screening.

Novel risk markers for gastric cancer screening: Present status and future prospects

Initial identification of populations at high risk of gastric cancer (GC) is important for endoscopic screening of GC. As serum pepsinogen (PG) test-positive subjects with progression of chronic atrophic gastritis (CAG) show a high likelihood of future cancer development, this population warrants careful follow-up observation as a high-risk GC group. By combining the PG test with Helicobacter pylori (HP) antibody titers, the HP-related chronic gastritis stage can be classified, thus identifying not only a GC high-risk group but also a low-risk group. Among PG test-negative patients without CAG, those with high serum PG Ⅱ levels and HP antibody titers are thought to have severe gastric mucosal inflammation and the risk of diffuse-type GC is also high. Meanwhile, in gastric mucosae obtained by endoscopic biopsy, HP infection induces aberrant DNA methylation in CpG islands in multiple gene regions and the extent of methylation clearly correlates with GC risk. By quantifying aberrant DNA methylation in suitable gene markers, we can determine the extent of the epigenetic field for cancerization. These novel concepts and risk markers will have many clinical applications in gastrointestinal endoscopy, including more efficient endoscopic GC screening and a strategic approach to metachronous multiple GCs after endoscopic treatment.

Non-invasive diagnosis of gastric mucosal atrophy in an asymptomatic population with high prevalence of gastric cancer

AIM: To validate a non-invasive method to detect gastric mucosal atrophy in a Chilean population with high prevalence of gastric cancer and a poor survival rate. METHODS: We first determined the optimal cut-off level of serum pepsinogen (PG)-1, PG-1/PG-2 ratio and 17-gastrin in 31 voluntary symptomatic patients (mean age: 66.1 years), of them 61% had histologically confirmed gastric atrophy. Then, in a population-based sample of 536 healthy individuals (209 residents in counties with higher relative risk and 327 residents in counties with lower relative risk for gastric cancer), we measured serum anti-H pylori antibodies, PG and 17-gastrin and estimated their risk of gastric cancer. RESULTS: We found that serum PG-1 < 61.5 μg/L, PG-1/PG-2 ratio < 2.2 and 17-gastrin > 13.3 pmol/L had a high specificity (91%-100%) and a fair sensitivity (56%-78%) to detect corpus-predominant atrophy. Based on low serum PG-1 and PG-1/PG-2 ratio together as diagnostic criteria, 12.5% of the asymptomatic subjects had corpus-predominant atrophy (0% of those under 25 years and 20.2% over 65 years old). The frequency of gastric atrophy was similar (12% vs 13%) but H pylori infection rate was slightly higher (77% vs 71%) in the high-risk compared to the low-risk counties. Based on their estimated gastric cancer risk, individuals were classified as: low-risk group (no H pylori infection and no atrophy; n = 115; 21.4%); moderate-risk group(H pylori infection but no atrophy; n = 354, 66.0%); and high-risk group (gastric atrophy, with or without H pylori infection; n = 67, 12.5%). The high-risk group was significantly older (mean age: 61.9 ± 13.3 years), more frequently men and less educated as compared with the low-risk group. CONCLUSION: We propose to concentrate on an upper gastrointestinal endoscopy for detection of early gastric cancer in the high-risk group. This intervention model could improve the poor prognosis of gastric cancer in Chile.

PGC-MG7 combination could be used as a follow-up panel for monitoring dynamical progression of gastric precancerous diseases

Objective: The aim of this study was to investigate the value of the combined expression of the gastric mucosal differentiation protein pepsinogen C(PGC) and gastric cancer(GC)-associated antigen MG7 for the diagnosis of GC and prediction of the development from precancerous conditions to GC.Methods: The gastric mucosal biopsies of 285 subjects enrolled from a region with a high incidence of GC were obtained and histopathologically examined. Subjects testing negative for GC(n=208) were followed up from 1998 to 2015. The levels of PGC and MG7 in the biopsies were determined by immunohistochemistry.Results: PGC was positive in 91.4% of the non-atrophic gastritis, 26.5% of the atrophic gastritis, and 0% of the GC. MG7 was positive in 15.0% of the non-atrophic gastritis, 82.4% of the atrophic gastritis, and 94.8% of the GC. The non-atrophic gastritis group was predominantly "PGC+MG7-". The atrophic gastritis and GC groups were predominantly "PGC-MG7+". The rate of GC in subjects with "PGC-MG7+" staining was 113.4-fold higher [95% confidence interval(95% CI): 15.3-869.4, P<0.001] than that in subjects with other staining patterns.The sensitivity and specificity of the "PGC-MG7+" pattern were 92.2% and 78.8% for the detection of GC and77.2% and 97.9% for GC and precancerous disease, respectively. In the follow-up cohort of non-GC subjects, the risk of developing GC was higher in those with the "PGC-MG7+" staining pattern.Conclusions: Our data suggest that the "PGC-MG7+" pattern can be employed as a useful follow-up panel for detecting individuals with a high risk of GC, and the dynamic assessment of the follow-up panel needs multi-centre large-scale validation in the future.

Predominant mucosal IL-8 mRNA expression in non-cagA Thais is risk for gastric cancer

AIM: To study gastric mucosal interleukine-8 (IL-8) mRNA expression, the cytotoxin-associated gene A (cagA) mutation, and serum pepsinogen (PG)?I/II ratio related risk in Thai gastric cancer.METHODS: There were consent 134 Thai non-cancer volunteers who underwent endoscopic narrow band imaging examination, and 86 Thais advance gastric cancer patients who underwent endoscopic mucosal biopsies and gastric surgery. Tissue samples were taken by endoscopy with 3 points biopsies. The serum PG?I, II, and Helicobacter pylori (H. pylori) immunoglobulin G (IgG) antibody for H. pylori were tested by enzyme-linked immunosorbent assay technique. The histopathology description of gastric cancer and non-cancer with H. pylori detection was defined with modified Sydney Score System. Gastric mucosal tissue H. pylori DNA was extracted and genotyped for cagA mutation. Tissue IL-8 and cyclooxygenase-2 (COX-2) mRNA expression were conducted by real time relative quantitation polymerase chain reaction. From 17 Japanese advance gastric cancer and 12 benign gastric tissue samples, all were tested for genetic expression with same methods as well as Thai gastric mucosal tissue samples. The multivariate analysis was used for the risk study. Correlation and standardized t-test were done for quantitative data, P value < 0.05 was considered as a statistically significant.RESULTS: There is a high non cagA gene of 86.8 per cent in Thai gastric cancer although there are high yields of the East Asian type in the positive cagA. The H. pylori infection prevalence in this study is reported by combined histopathology and H. pylori IgG antibody test with 77.1% and 97.4% of sensitivity and specificity, respectively. The serum PG?I/II ratio in gastric cancer is significantly lower than in the non-cancer group, P = 0.045. The serum PG?I/II ratio of less than 3.0 and IL-8 mRNA expression ≥ 100 or log10 ≥ 2 are significant cut off risk differences between Thai cancer and non-cancer, P = 0.03 and P < 0.001, respectively. There is a significantly lower PGI/II ratio in Japanese than that in Thai gastric cancer, P = 0.026. Serum PG?I/II ratio at cut off less than 3.0 and IL-8 mRNA expression Raw RQ > 100 or log10 > 2 are significantly difference between Thai cancer group when compared to non-cancer group, P = 0.013 and P < 0.001, respectively. In the correlation study, low PG?I/II ratio does not associate with chronic atrophic gastritis severity score in Thais non-cancer cases. However, there is a trend, but not significant convert correlation between IL-8 mRNA expression level and low PG?I/II ratio in Thai positive H. pylori infection. The high expression of IL-8 gene demonstrates a poorer prognosis by stage and histology.CONCLUSION:Predominant gastric mucosal IL-8 mRNA expression level, H. pylori infection, and low PG?I/II ratio are relative risks for Thai gastric cancer without correlation with cagA mutation.