Simultaneous detection of different serum pepsinogens and its primary application

AIM: To develop the simple, rapid and sensitive dual-label time-resolved fluoroimmunoassay for pepsinogens in human serum.METHODS: Based on two-site sandwich protocol, mono-clonal antibodies (McAbs) against pepsinogen Ⅰ (PG Ⅰ) and PG Ⅱ were co-coated in 96 microtitration wells, and tracer McAbs against PG Ⅰ and PG Ⅱ were labeled with europium (Eu) and samarium (Sm) chelate, respectively. Diluted serum samples of Eu3+- and Sm3+-McAbs were added into microtitration wells simultaneously. After washing, fluorescence of bound Sm3+ and Eu3+ tracers was detected. RESULTS: The detection limit was 0.2 μg/L for PG Ⅰ and 0.05 μg/L for PG Ⅱ. The assay range was 5.0-320.0 μg/Lfor PG Ⅰ and 1.0-55.0 μg/L for PG Ⅱ. The average re-covery rate was 102.7% for PG Ⅰ and 98.8% for PG Ⅱ. Sera from healthy controls and patients with gastric dis-ease were analyzed. The PG detected by dual-label as-say was in good agreement with that detected by single-label assay or by enzyme-linked immunosorbent assay. CONCLUSION: Dual-label assay can provide high-throughput serological screening for gastric diseases.

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.

Clinical value of serum pepsinogen in the diagnosis and treatment of gastric diseases

Pepsinogen,secreted from the gastric mucosa,is the precursor of pepsin.It is categorized as pepsinogen 1 and pepsinogen 2 based on its immunogenicity.The pepsinogen content that can enter the blood circulation through the capillaries of the gastric mucosa is approximately 1%and remains stable all the time.The pepsinogen content in serum will change with the pathological changes of gastric mucosa.Therefore,the level of pepsinogen in serum can play a role in serologic biopsy to reflect the function and morphology of different regions of gastric mucosa and serve as an indicator of gastric disease.This study conducts relevant research on serum pepsinogen 1,pepsinogen 2,and the ratio of pepsinogen 1 to pepsinogen 2,and reviews their important value in clinical diagnosis of Helicobacter pylori infection,gastric ulcer,and even gastric carcinoma,providing ideas for other researchers.

The ontogeny of acidic digestive tract in larval turbot Scophthalmus maximus based on H+/K+-ATPase and pepsinogen

Acidic digestion is an important digestive process of marine fish.In fish stomach,two enzymes are involved in the secretion of hydrochloric acid(HCl)and proteomic digestion:H^(+)/K^(+)-ATPase and pepsinogen.However,the starting of digestive function in fish is still unclear.To reveal the details of acidic digestion of turbot Scophthalmus maximus in early development,a 40 day of turbot larvae culture was conducted.The H^(+)/K^(+)-ATPase gene from the turbot S.maximus(smH^(+)/K^(+)-ATPase)was identified and characterized.Based on our previous discription on pepsinogen of turbot S.maximus,we combined pepsinogen and H^(+)/K^(+)-ATPase and analyzed the mechanism of acidic digestion in turbot.Results show that the spatial and temporal expression profiles of H^(+)/K^(+)-ATPase agreed with pepsinogen A and C in turbot,indicating a synergetic action between H^(+)/K^(+)-ATPase and pepsinogen during the acidic digestion process.In addition,the turbot juveniles showed a faster growth after the expressions of H^(+)/K^(+)-ATPase gene and pepsinogen gene,demonstrating that pepsin had a higher digestive efficiency,for which a compound diet should be provided to the fish from Day 22 onward.This study provided a reference for biology research and aquaculture of turbot and other marine fishes.

Helicobacter pylori-related chronic gastritis as a risk factor for colonic neoplasms

To summarize the current views and insights on associations between Helicobacter pylori(H. pylori)-related chronic gastritis and colorectal neoplasm, we reviewed recent studies to clarify whether H. pylori infection/H. pylori-related chronic gastritis is associated with an elevated risk of colorectal neoplasm. Recent studies based on large databases with careful control for confounding variables have clearly demonstrated an increased risk of colorectal neoplasm associated with H. pylori infection. The correlation between H. pylori-related chronic atrophic gastritis(CAG) and colorectal neoplasm has only been examined in a limited number of studies. A recent large study using a national histopathological database, and our study based on the stage of H. pylori-related chronic gastritis as determined by serum levels of H. pylori antibody titer and pepsinogen, indicatedthat H. pylori-related CAG confers an increased risk of colorectal neoplasm, and more extensive atrophic gastritis will probably be associated with even higher risk of neoplasm. In addition, our study suggested that the activity of H. pylori-related chronic gastritis is correlated with colorectal neoplasm risk. H. pylori-related chronic gastritis could be involved in an increased risk of colorectal neoplasm that appears to be enhanced by the progression of gastric atrophy and the presence of active inflammation.

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.

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.

Changes with aging in gastric biomarkers levels and in biochemical factors associated with Helicobacter pylori infection in asymptomatic Chinese population

AIM To observe changes in gastric biomarker levels with age and effects of Helicobacter pylori(H. pylori) infection in a healthy population, and explore factors associated with gastric biomarkers.METHODS Three hundred and ninety-five subjects were selected and underwent physical examinations, biochemical tests, and measurement of serum pepsinogen(PG)Ⅰ and Ⅱ, gastrin-17(G-17) and H. pylori antibody levels. Analyses were made by Student's t-test, ANOVA, Pearson's correlation and multiple linear regressions.RESULTS PGII levels were higher in the ≥ 65-years-old age group(P < 0.05) and PGI/PGII were lower in the ≥ 75-years-old age group(P = 0.035) compared to the 35-44-years-old age group. Levels of low-density lipoprotein cholesterol(LDL-C) were higher(P = 0.009) in H. pylori-infected subjects that were male. LDL-C levels were higher in 55-74-years-old age group(P < 0.05) for H. pylori-infected subjects and 45-64-yearsold age group(P < 0.05) for non-infected subjects compared to 35-44-years-old age group. Hp-Ig G level positively correlated with PGⅠ, PGⅡ and G-17(P < 0.001, P < 0.001, P = 0.006), and negatively correlated with PGI/PGII(P < 0.001). Creatinine positively correlated with PGⅠ, PGⅡ and G-17(P < 0.001, P < 0.001, P < 0.001). Fasting blood glucose(FBG) positively correlated with PGⅠ/PGⅡ and G-17(P < 0.001, P = 0.037). Age positively correlated with PGII and G-17(P = 0.005, P = 0.026).CONCLUSION PGII levels increased while PGI/PGII declined with age in a healthy population. H. pylori infection had an effect on raising LDL-C levels to increase the risk of atherosclerosis in males, especially those of elderly age. Age, H. pylori infection, levels of renal function and FBG were associated with levels of pepsinogens and gastrin.

First-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced by CYP2C19 genotype

AIM: To evaluate the effect of first line esomeprazole(EPZ)-based triple therapy on Helicobacter pylori(H. pylori) eradication.METHODS: A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or ^(13)C-urea breath tests were included in this study. The average age of the patients was 57.2 years(male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen(PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry(UMIN000009642).RESULTS: The H. pylori eradication rates by EPZbased triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors(PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer(EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM(P < 0.05). The serum PG?Ⅰ?level and PG?Ⅰ/Ⅱ ratio were significantly increased after eradication of H. pylori(P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZbased triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other firstgeneration PPIs in the Japanese population.CONCLUSION: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other firstgeneration PPIs.

Prevalence of Helicobacter pylori infection and atrophic gastritis in patients with dyspeptic symptoms in Myanmar

AIM: To survey the detailed analyses for Helicobacter pylori(H. pylori) infection and gastric mucosal status in Myanmar.METHODS: A total of 252 volunteers with dyspeptic symptoms(155 female and 97 male; mean age of 43.6 ± 14.2 years) was participated in Yangon and Mandalay. The status of H. pylori infection was determined based on 5 different tests including rapid urease test, culture, histology, immunohistochemistry and serology. Histological scores were evaluated according to the update Sydney system and the Operative Link for Gastritis Assessment system. Pepsinogen(PG)Ⅰand PG Ⅱ were measured using enzyme-linked immunosorbent assays.RESULTS: The overall prevalence of H. pylori infectionwas 48.0%. There was no relationship between age and infection rate. Even in young group(less than 29 years old), the H. pylori infection rate was relatively high(41.9%). The prevalence of H. pylori infection was significantly higher in Yangon than that of Mandalay. H. pylori infection was significantly associated with the presence of gastric mucosal atrophy. All 7 subjects with peptic ulcer were infected with H. pylori. Although H. pylori-positive subjects showed stronger gastritis than H. pylori-negative subjects, most cases had mild gastritis.CONCLUSION: We revealed the prevalence of H. pylori infection in patients with dyspeptic symptoms in Myanmar. The H. pylori infection was a risk factor for peptic ulcer and stronger gastritis.

Standard vs magnifying narrow-band imaging endoscopy for diagnosis of Helicobacter pylori infection and gastric precancerous conditions

BACKGROUND Advances in endoscopic imaging enable the identification of patients at high risk of gastric cancer.However,there are no comparative data on the utility of standard and magnifying narrow-band imaging(M-NBI)endoscopy for diagnosing Helicobacter pylori(H.pylori)infection,gastric atrophy,and intestinal metaplasia.AIM To compare the diagnostic performance of standard and M-NBI endoscopy for H.pylori gastritis and precancerous conditions.METHODS In 254 patients,standard endoscopy findings were classified into mosaic-like appearance(type A),diffuse homogenous redness(type B),and irregular redness with groove(type C).Gastric mucosal patterns visualized by M-NBI were classified as regular round pits with polygonal sulci(type Z-1),more dilated and linear pits without sulci(type Z-2),and loss of gastric pits with coiled vessels(type Z-3).RESULTS The diagnostic accuracy of standard and M-NBI endoscopy for H.pylori gastritis was 93.3%and 96.1%,respectively.Regarding gastric precancerous conditions,the accuracy of standard and M-NBI endoscopy was 72.0%vs 72.6%for moderate to severe atrophy,and 61.7%vs.61.1%for intestinal metaplasia in the corpus,respectively.Compared to type A and Z-1,types B+C and Z-2+Z-3 were significantly associated with moderate to severe atrophy[odds ratio(OR)=5.56 and 8.67]and serum pepsinogen I/II ratio of≤3(OR=4.48 and 5.69).CONCLUSION Close observation of the gastric mucosa by standard and M-NBI endoscopy is useful for the diagnosis of H.pylori gastritis and precancerous conditions.

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.

Family-based Helicobacter pylori infection status and transmission pattern in central China,and its clinical implications for related disease prevention

BACKGROUND Helicobacter pylori(H.pylori)has characteristics of family cluster infection;however,its family-based infection status,related factors,and transmission pattern in central China,a high-risk area for H.pylori infection and gastric cancer,have not been evaluated.We investigated family-based H.pylori infection in healthy households to understand its infection status,related factors,and patterns of transmission for related disease prevention.AIM To investigate family-based H.pylori infection status,related factors,and patterns of transmission in healthy households for related disease prevention.METHODS Blood samples and survey questionnaires were collected from 282 families including 772 individuals.The recruited families were from 10 selected communities in the greater Zhengzhou area with different living standards,and the family members’general data,H.pylori infection status,related factors,and transmission pattern were analyzed.H.pylori infection was confirmed primarily by serum H.pylori antibody arrays;if patients previously underwent H.pylori eradication therapy,an additional 13C-urea breath test was performed to obtain their current infection status.Serum gastrin and pepsinogens(PGs)were also analyzed.RESULTS Among the 772 individuals examined,H.pylori infection rate was 54.27%.These infected individuals were from 246 families,accounting for 87.23%of all 282 families examined,and 34.55%of these families were infected by the same strains.In 27.24%of infected families,all members were infected,and 68.66%of them were infected with type I strains.Among the 244 families that included both husband and wife,spouse co-infection rate was 34.84%,and in only 17.21%of these spouses,none were infected.The infection rate increased with duration of marriage,but annual household income,history of smoking,history of alcohol consumption,dining location,presence of gastrointestinal symptoms,and family history of gastric disease or GC did not affect infection rates;however,individuals who had a higher education level showed lower infection rates.The levels of gastrin-17,PGI,and PGII were significantly higher,and PGI/II ratio was significantly lower in H.pylori-infected groups than in H.pylori-negative groups.CONCLUSION In our study sample from the general public of central China,H.pylori infection rate was 54.27%,but in 87.23%of healthy households,there was at least 1 H.pylori-infected person;in 27.24%of these infected families,all members were infected.Type I H.pylori was the dominant strain in this area.Individuals with a higher education level showed significantly lower infection rates;no other variables affected infection rates.

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 log 10 ≥ 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 log 10 > 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.

Metachronous gastric cancer after successful Helicobacter pylori eradication

The high incidence of gastric cancer in Japan initially resulted in establishment of a country-wide gastric cancer screening program to detect early and treatable cancers. In 2013 countrywide Helicobacter pylori(H. pylori) eradication was approved coupled with endoscopy to assess for the presence of chronic gastritis. Current data support the notion that cure of the infection in those with non-atrophic gastritis will prevent development of gastric cancer. However, while progression to more severe damage is halted in those who have already developed, atrophic gastritis/gastric atrophy remain at risk for subsequent development of gastric cancer. That risk is directly related to the extent and severity of atrophic gastritis. Methods to stratify cancer risk include those based on endoscopic assessment of the atrophic border, histologic grading, and non-invasive methods based on serologic testing of pepsinogen levels. Continued surveillance is required because those with atrophic gastritis/gastric atrophy retain considerable gastric cancer risk even after H. pylori eradication. Those who have already experienced a resectable early gastric cancer are among those at highest risk as metachronous lesions are frequent even after H. pylorieradication. We review the role of H. pylori and effect of H. pylori eradication indicating the incidence and the predictive factors on development of metachronous cancer after endoscopic therapy of early gastric cancer. Studies to refine risk markers to stratify for risk, surveillance methods, intervals, and duration after successful H. pylori eradication, and whether adjuvant therapy would change risk are needed.

Serum gastrin-17 concentration for prediction of upper gastrointestinal tract bleeding risk among peptic ulcer patients

BACKGROUND Serum gastrin-17(G-17),pepsinogen I(PGI),and pepsinogen II(PGII)concentrations regulate gastric acid secretion,and hypersecretion of gastric acid increases the risks of peptic ulcer and upper gastrointestinal bleeding.These associations suggest that serum G-17,PGI,and(or)PGII may predict gastrointestinal bleeding risk among peptic ulcer patients.AIM To evaluate the efficacies of serum G-17,PGI,PGII,and PGI/PGII ratio(PGR)for predicting upper gastrointestinal bleeding among peptic ulcer patients.METHODS A total of 199 patients diagnosed with peptic ulcer confirmed by gastroscopy and positivity for Helicobacter pylori by the 14C-urea breath test were recruited,including 107 patients with simple peptic ulcer and 92 cases complicated by upper gastrointestinal bleeding.Serum PGI,PGII,G-17,and PGR were measured by immune methods and compared between bleeding and non-bleeding groups by univariate analysis.The specificity and sensitivity of PGs and G-17 for evaluating upper gastrointestinal bleeding risk were then assessed by constructing receiver operating characteristic(ROC)curves.RESULTS Serum G-17 was significantly higher among peptic ulcer patients with upper gastrointestinal bleeding compared to simple peptic ulcer patients(25.34±14.29 vs 8.84±8.03 pmol/L,t=9.822,P<0.01),whereas serum PGI,PGII,and PGR did not differ significantly between bleeding and non-bleeding groups(all P>0.05).The risk of bleeding was significantly higher among peptic ulcer patients with elevated serum G-17(>15 pmol/L)compared to patients with normal or low serum G-17(73.2%vs 27.4%,χ2=40.72,P<0.01).The area under the ROC curve for serum G-17 was 0.866±0.024,and a cut-off of 9.86 pmol/L yielded 90.2%sensitivity and 68.2%specificity for distinguishing peptic ulcer with and without upper gastrointestinal bleeding.CONCLUSION Serum G-17 is significantly upregulated in peptic ulcer patients and higher levels are predictive of upper gastrointestinal bleeding.Conversely,serum PGI,PGII,and PGR have no predictive value.Further prospective studies are warranted to examine if high G-17 can be used to assess risk of bleeding prior to onset.

Gastric adenocarcinoma of fundic gland type spreading to heterotopic gastric glands

Herein, we present a case of gastric adenocarcinoma of fundic gland type(GA-FG) spreading to heterotopic gastric glands(HGG) in the submucosa. A 58-year-old man with epigastric pain was referred to our hospital and underwent an esophagogastroduodenoscopy. A Borrmann type II gastric cancer at the antrum and a 10 mm submucosal tumor-like lesion in the lesser curvature of the upper third of the stomach were detected. Histological examination of the biopsy specimens obtained from the submucosal tumorlike lesion suggested a GA-FG. Therefore, endoscopic submucosal dissection was performed as excisional biopsy, and histopathological examination of the resected specimen confirmed a GA-FG and HGG proximal to the GA-FG. Although the GA-FG invaded the submucosal layer slightly, the submucosal lesion of the GA-FG had a poor stromal reaction and was located just above the HGG in the submucosa. Therefore, wefinally diagnosed the lesion as a GA-FG invading the submucosal layer by spreading to HGG.

CONTRASTIVE STUDY OF THE TISSUE EXPRESSION AND SERUM CONCENTRATION OF PEPSINOGEN C IN GASTRIC MUCOSA DISEASES

Objective： To estimate the practical values of pepsinogen C （PGC） dynamic expression and the levels of serum pepsinogens in gastric cancer screening and diagnosis. Methods： 129 cases gastric mucosa biopsies and serum specimens were examined. The expression of PGC in stomach mucosa was detected by immunohistochemistry. The serum concentration of pepsinogen A （sPGA） and pepsinogen C （sPGC） were determined by ELISA. Results： The positive rate of PGC antigen expression decreased in superficial gastritis （100%）, gastric ulcer or erosion （80.00%）, atrophic gastritis （34.48%） and gastric cancer （11.43%） in sequence （P〈0.05）. There was no statistics difference in concentration of sPGA and sPGC among the above 4 groups. The ratio of sPGA/sPGC decreased in superficial gastritis, gastric ulcer or erosion, atrophic gastritis and gastric cancer in sequence （P〈0.05）. There was specific correlation between the expression of PGC in stomach mucosa and the levels of sPGA/sPGC ratio in serum （rs =0.297, P=0.001）. Conclusion： Tissue expression of PGC has close relationship with different gastric diseases. The ratio of sPGA/sPGC is relative with the tissue expression of PGC antigen and may be a convenient and economic maker in screening and diagnosis of gastric cancer.

Inverse correlation between gastroesophageal reflux disease and atrophic gastritis assessed by endoscopy and serology

BACKGROUND Helicobacter pylori(H.pylori)infection is known to prevent the occurrence of gastroesophageal reflux disease(GERD)by inducing gastric mucosal atrophy.However,little is known about the relationship between atrophic gastritis(AG)and GERD.AIM To confirm the inverse correlation between AG and the occurrence and severity of GERD.METHODS Individuals receiving health checkups who underwent upper gastrointestinal endoscopy at Seoul National University Healthcare System Gangnam Center were included.The grade of reflux esophagitis was evaluated according to the Los Angeles classification.Endoscopic AG(EAG)was categorized into six grades.Serologic AG(SAG)was defined as pepsinogen I≤70 ng/m L and pepsinogen I/II ratio≤3.0.The association between the extent of EAG and SAG and the occurrence and severity of GERD was evaluated using multivariate logistic regression analysis.RESULTS In total,4684 individuals with GERD were compared with 21901 healthy controls.In multivariate logistic regression analysis,advanced age,male sex,body mass index>23 kg/m2,presence of metabolic syndrome,current smoking,and alcohol consumption were associated with an increased risk of GERD.Seropositivity for H.pylori immunoglobulin G antibodies was associated with a decreased risk of GERD.There was an inverse correlation between the extent of EAG and occurrence of GERD:Odds ratio(OR),1.01[95%confidence interval(CI):0.90-1.14]in C1,0.87(0.78-0.97)in C2,0.71(0.62-0.80)in C3,0.52(0.44-0.61)in O1,0.37(0.29-0.48)in O2,and 0.28(0.18-0.43)in O3.Additionally,the extent of EAG showed an inverse correlation with the severity of GERD.The presence of SAG was correlated with a reduced risk of GERD(OR=0.49,95%CI:0.28-0.87,P=0.014).CONCLUSION The extent of EAG and SAG exhibited strong inverse relationships with the occurrence and severity of GERD.AG followed by H.pylori infection may be independently protect against GERD.

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.