Comparison of operative link for gastritis assessment, operative link on gastric intestinal metaplasia assessment, and TAIM stagings among men with atrophic gastritis

BACKGROUND Gastric cancer is the world’s third most lethal malignancy. Most gastric cancers develop through precancerous states of atrophic gastritis and intestinal metaplasia. Two staging systems, operative link for gastritis assessment(OLGA)and operative link on gastric intestinal metaplasia assessment(OLGIM), have been developed to detect high gastric cancer risk. European guidelines recommend surveillance for high-risk OLGA/OLGIM patients(stages Ⅲ–Ⅳ),and for those with advanced stage of atrophic gastritis in the whole stomach mucosa. We hypothesize, that by combining atrophy and intestinal metaplasia into one staging named TAIM, more patients with increased gastric cancer risk could be detected.AIM To evaluate the clinical value of the OLGA, OLGIM, and novel TAIM stagings as prognostic indicators for gastric cancer.METHODS In the Helsinki Gastritis Study, 22346 elderly male smokers from southwestern Finland were screened for serum pepsinogen I(PGI). Between the years 1989 and1993, men with low PGI values(PGI < 25 μg/L), were invited to undergo an oesophagogastroduodenoscopy. In this retrospective cohort study, 1147 men that underwent gastroscopy were followed for gastric cancer for a median of 13.7 years, and a maximum of 27.3 years. We developed a new staging system, TAIM,by combining the topography with the severity of atrophy or intestinal metaplasia in gastric biopsies. In TAIM staging, the gastric cancer risk is classified as low or high.RESULTS Twenty-eight gastric cancers were diagnosed during the follow-up, and the incidence rate was 1.72 per 1000 patient-years. The cancer risk associated positively with TAIM [Hazard ratio(HR) 2.70, 95%CI: 1.09–6.69, P = 0.03]. The risk increased through OLGIM stages 0-Ⅳ(0 vs Ⅳ: HR 5.72, 95%CI: 1.03–31.77, P for trend = 0.004), but not through OLGA stages 0–Ⅳ(0 vs Ⅳ: HR 5.77, 95%CI:0.67–49.77, P for trend = 0.10). The sensitivities of OLGA and OLGIM stages Ⅲ–Ⅳ were low, 21% and 32%, respectively, whereas that of TAIM high-risk was good, 79%. On the contrary, OLGA and OLGIM had high specificity, 85% and81%, respectively, but TAIM showed low specificity, 42%. In all three staging systems, the high-risk men had three-to four-times higher gastric cancer risk compared to the general male population of the same age.CONCLUSION OLGIM and TAIM stagings show prognostic value in assessing gastric cancer risk in elderly male smokers with atrophic gastritis.

Non-sequential narrow band imaging for targeted biopsy and monitoring of gastric intestinal metaplasia

AIM： To evaluate the efficacy of non-sequential narrow band imaging （NBI） for a better recognition of gastric intestinal metaplasia （GIM）. METHODS： Previously diagnosed GIM patients underwent targeted biopsy from areas with and without GIM, as indicated by NBI, twice at an interval of 1 year. The authors compared the endoscopic criteria such as light blue crest （LBC）, villous pattern （VP）, and large long crest （LLC） with standard histology. The results from two surveillance endoscopies were compared with histology results for sensitivity, specificity, positive predic-tive value （PPV）, negative predictive value （NPV）, and likelihood ratio of positive test （LR＋）. The number of early gastric cancer cases detected was also reported. RESULTS： NBI targeted biopsy was performed in 38 and 26 patients during the first and second surveillance endoscopies, respectively. There were 2 early gastric cancers detected in the first endoscopy. No cancer was detected from the second study. Surgical and endoscopic resections were successfully performed in each patient. Sensitivity, specificity, PPV, NPV, and LR＋ of all 3 endoscopic criteria during the first/second surveillances were 78.8%/91.3%, 82.5%/89.1%, 72.8%/77.8%, 86.8%/96.1, and 4.51/8.4, respectively. LBC provided the highest LR＋ over VP and LLC. CONCLUSION： Nonequential NBI is useful for GIM targeted biopsy. LBC provides the most sensitive reading. However, the optimal duration between two surveillances requires further study.

Comparison of white-light endoscopy,optical-enhanced and aceticacid magnifying endoscopy for detecting gastric intestinal metaplasia:A randomized trial

BACKGROUND Gastric intestinal metaplasia(GIM)is a precancerous lesion of the stomach,which severely affects human life and health.Currently,a variety of endoscopic techniques are used to screen/evaluate GIM.Traditional white-light endoscopy(WLE)and acetic-acid chromoendoscopy combined with magnifying endoscopy(MEAAC)are the interventions of choice due to their diagnostic efficacy for GIM.Optical-enhanced magnifying endoscopy(ME-OE)is a new virtual chromoendoscopy technique to identify GIM,which combines bandwidth-limited light and image enhancement processing technology to enhance the detection of mucosal and vascular details.We hypothesized that ME-OE is superior to WLE and MEAAC in the evaluation of GIM.AIM To directly compare the diagnostic value of WLE,ME-AAC,and ME-OE for detection of GIM.METHODS A total of 156 patients were subjected to consecutive upper gastrointestinal endoscopy examinations using WLE,ME-AAC,and ME-OE.Histopathological findings were utilized as the reference standard.Accuracy,sensitivity,specificity,and positive and negative predictive values of the three endoscopy methods in the diagnosis of GIM were evaluated.Moreover,the time to diagnosis with MEAAC and ME-OE was analyzed.Two experts and two non-experts evaluated the GIM images diagnosed using ME-OE,and diagnostic accuracy and intra-and inter-observer agreement were analyzed.RESULTS GIM was detected in 68 of 156 patients(43.6%).The accuracy of ME-OE was highest(91.7%),followed by ME-AAC(86.5%),while that of WLE(51.9%)was lowest.Per-site analysis showed that the overall diagnostic accuracy of ME-OE was higher than that of ME-AAC(P=0.011)and WLE(P<0.001).The average diagnosis time was lower in ME-OE than in ME-AAC(64±7 s vs 151±30 s,P<0.001).Finally,the inter-observer agreement was strong for both experts(k=0.862)and non-experts(k=0.800).The internal consistency was strong for experts(k=0.713,k=0.724)and moderate for non-experts(k=0.667,k=0.598).CONCLUSION For endoscopists,especially experienced endoscopists,ME-OE is an efficient,convenient,and time-saving endoscopic technique that should be used for the diagnosis of GIM.

Gastric intestinal metaplasia development in African American predominant United States population

BACKGROUND Gastric cancer significantly contributes to cancer mortality globally.Gastric intestinal metaplasia(GIM)is a stage in the Correa cascade and a premalignant lesion of gastric cancer.The natural history of GIM formation and progression over time is not fully understood.Currently,there are no clear guidelines on GIM surveillance or management in the United States.AIM To investigate factors associated with GIM development over time in African American-predominant study population.METHODS This is a retrospective longitudinal study in a single tertiary hospital in Washington DC.We retrieved upper esophagogastroduodenoscopies(EGDs)with gastric biopsies from the pathology department database from January 2015 to December 2020.Patients included in the study had undergone two or more EGDswith gastric biopsy.Patients with no GIM at baseline were followed up until they developed GIM or until the last available EGD.Exclusion criteria consisted of patients age<18,pregnancy,previous diagnosis of gastric cancer,and missing data including pathology results or endoscopy reports.The study population was divided into two groups based on GIM status.Univariate and multivariate Cox regression was used to estimate the hazard induced by patient demographics,EGD findings,and Helicobacter pylori(H.pylori)status on the GIM status.RESULTS Of 2375 patients who had at least 1 EGD with gastric biopsy,579 patients were included in the study.138 patients developed GIM during the study follow-up period of 1087 d on average,compared to 857 d in patients without GIM(P=0.247).The average age of GIM group was 64 years compared to 56 years in the non-GIM group(P<0.001).In the GIM group,adding one year to the age increases the risk for GIM formation by 4%(P<0.001).Over time,African Americans,Hispanic,and other ethnicities/races had an increased risk of GIM compared to Caucasians with a hazard ratio(HR)of 2.12(1.16,3.87),2.79(1.09,7.13),and 3.19(1.5,6.76)respectively.No gender difference was observed between the study populations.Gastritis was associated with an increased risk for GIM development with an HR of 1.62(1.07,2.44).On the other hand,H.pylori infection did not increase the risk for GIM.CONCLUSION An increase in age and non-Caucasian race/ethnicity are associated with an increased risk of GIM formation.The effect of H.pylori on GIM is limited in low prevalence areas.

Bile reflux and bile acids in the progression of gastric intestinal metaplasia

Gastric intestinal metaplasia(GIM)is a precancerous lesion of gastric cancer(GC)and is considered an irreversible point of progression for GC.Helicobacter pylori infection can cause GIM,but its eradication still does not reverse the process.Bile reflux is also a pathogenic factor in GIM and can continuously irritate the gastric mucosa,and bile acids in refluxed fluid have been widely reported to be associated with GIM.This paper reviews in detail the relationship between bile reflux and GIM and the mechanisms by which bile acids induce GIM.

Microsatellite Instability in Intestinal Metaplasia and Gastric Cancer

Objective: To investigate the changeable patterns of microsatellite instability(MSI)in intestinal metaplasia(IM)and gastric cancer(GC)and the role of MSI in gastric carcinogenesis. Methods: Silver staining single strand conformation polymorphism-polymeriase chain reaction(PCR-SSCP)was used to screen MSI markers at 5 loci in formalin-fixed,paraffin-embedded tissues of GC(n=30),IM(n=40)and corresponding normal gastric tissues. Results: The abnormal shifting of the single-strand DNA was identified in 7(23.3%)out of GC and in 8(20%)out of IM samples.Three(10%)tumors and one(2.5%)IM displayed high-frequency MSI(two or more loci altered).Low-frequency MSI(one loci altered)was detected in 4(13.3%)of the tumors and in 7(17.5%)IM samples.GC with MSI was associated with distal location of the tumors but age,sex,differentiation,lymph nodes metastasis and TNM stage(P=0.044).MSI was more likely detected in moderate-grade IM than in mild-grade IM tissues(34.8% versus 0; P=0.013); and MSI had a tendency to be easily detected in female with IM. Conclusion: The progressive accumulation of MSI in areas of IM may contribute to GC development,representing an important molecular event in the multistep gastric carcinogenesis.

Lamb’s tripe extract and vitamin B12 capsule plus celecoxib reverses intestinal metaplasia and atrophy:A retrospective cohort study

BACKGROUND Chronic atrophic gastritis(AG)with intestinal metaplasia(IM)significantly increases the risk of gastric cancer.Some medicines have showed definite therapeutic effects in AG and IM regression.AIM To validate the efficacy of Lamb’s tripe extract and vitamin B12 capsule(LTEVB12)initial therapy and celecoxib rescue therapy for IM and AG.METHODS A total of 255 patients were included to receive LTEVB12 initial therapy(2 capsules each time,three times daily for 6 mo)in hospital in this study.The patients with failure of IM regression continued to receive celecoxib rescue therapy(200 mg,once daily for 6 mo).After each therapy finished,the patients underwent endoscopy and biopsy examination.The regression efficiency was assessed by the operative link on gastritis assessment(OLGA)and the operative link on the gastric intestinal metaplasia assessment(OLGIM)staging system.Logistic regression analysis was applied to identify factors associated with the curative effect.RESULTS For LTEVB12 initial therapy,the reversal rates of IM and AG were 52.95%and 48.24%,respectively.Analogously,for celecoxib rescue therapy,the effective rates for IM and AG were 56.25%and 51.56%,respectively.The IM regression rate of complete therapy was up to 85.03%.In different OLGA and OLGIM stages of IM patients,therapeutic efficiency showed a significant difference in each group(P<0.05).For both therapies,patients with high stages(III or IV)of both the OLGA and OLGIM evaluation systems showed a higher IM or AG regression rate than those with low stages(I or II).Among patients with high stages(OLGIM III and IV),the IM regression rate was above 70%for each therapy.Eating habits,fresh vegetable intake,and high-salt diet were identified as independent factors for the IM reversal effect of LTEVB12 therapy,especially high-salt diet(odds ratio=1.852,P<0.05).CONCLUSION Monotherapy could reverse IM and AG.LTEVB12 initial therapy and celecoxib rescue therapy significantly increase the regression effect.IM may not be the point of no return among gastric precancerous lesions.

Operative link on gastritis assessment stage is an appropriate predictor of early gastric cancer

AIM: To assess the predictive value of Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stages in gastric cancer.METHODS: A prospective study was conducted with 71 patients with early gastric cancer (EGC) and 156 patients with non-EGC. All patients underwent endoscopic examination and systematic biopsy. Outcome measures were assessed and compared, including the Japanese endoscopic gastric atrophy (EGA) classification method and the modified OLGA method as well as the modified OLGIM method. Helicobacter pylori (H. pylori) status was determined for all study participants. Stepwise logistic regression modeling was performed to analyze correlations between EGC and the EGA, OLGA and OLGIM methods.RESULTS: For patients with EGC and patients with non-EGC, the proportions of moderate-to-severe EGA cases were 64.8% and 44.9%, respectively (P = 0.005), the proportions of OLGA stages III-IV cases were 52.1% and 22.4%, respectively (P &#x0003c; 0.001), and the proportions of OLGIM stages III-IV cases were 42.3% and 19.9%, respectively (P &#x0003c; 0.001). OLGA stage and OLGIM stage were significantly related to EGA classification; specifically, logistic regression modeling showed significant correlations between EGC and moderate-to-severe EGA (OR = 1.95, 95% CI: 1.06-3.58, P = 0.031) and OLGA stages III-IV (OR = 3.14, 95%CI: 1.71-5.81, P &#x0003c; 0.001), but no significant correlation between EGC and OLGIM stages III-IV (P = 0.781). H. pylori infection rate was significantly higher in patients with moderate-to-severe EGA (75.0% vs 54.1%, P = 0.001) or OLGA/OLGIM stages III-IV (OLGA: 83.6% vs 55.8%, P &#x0003c; 0.001; OLGIM: 83.6% vs 57.8%, P &#x0003c; 0.001).CONCLUSION: OLGA classification is optimal for EGC screening. A surveillance program including OLGA stage and H. pylori infection status may facilitate early detection of gastric cancer.

Clinical features of gastric adenoma detected within 3 years after negative screening endoscopy in Korea

Background:Early detection and management of gastric adenoma are important for preventing gastric cancer.The present study aimed to evaluate the predictors of missed gastric adenoma on screening endoscopy in Korea and identify the risk factors associated with interval precancerous gastric lesions.Methods:All cases of gastric adenomas diagnosed via screening endoscopy between 2007 and 2019 were reviewed.Among them,those who had undergone endoscopy within 3 years were included in the present study.Missed gastric adenoma was defined as gastric adenoma diagnosed within 3 years after negative screening endoscopy.Results:In total,295 cases of gastric adenoma were identified.Of these,95(32.2%)were missed gastric adenoma cases(mean age,60.6 years;average interval between final and index endoscopies,12.6months);the remaining 200(67.8%)were newly detected adenoma cases.Univariate analysis revealed thatmale sex,endoscopist experience,observation time,and presence of gastric intestinalmetaplasia(pathologically proven)were associated with missed gastric adenoma.Multivariate analysis revealed that gastric intestinal metaplasia(odds ratio[OR],2.736;95%confidence interval[CI],1.320–5.667;P=0.007)and shorter observation time of the index screening endoscopy(B,0.011;OR,0.990;95%CI,0.986–0.993;P<0.001)were independent risk factors for missed gastric adenoma.The optimal cut-off for the observation time for detecting gastric adenoma was 3.53minutes(area under curve,0.738;95%CI,0.677–0.799;P<0.001).Conclusions:Gastric intestinal metaplasia is an indication of missed gastric adenoma.Therefore,careful inspection of gastric mucosa with gastric intestinal metaplasia and proper observation time can lower the possibility of missing the gastric adenoma during screening.

Clinical Study on the Piweiping Capsule (脾胃平胶囊) in TreatingPatients with Metaplasia of Gastric Mucosa

Objective: To evaluate the therapeutic effect of Piweiping capsule (PWPC) in treating patients with metaplasia of gastric mucosa and explore its mechanism. Method: One hundred and forty-three patients were diagnosed as chronic superficial atrophic gastritis of gastric antrum or with metaplasia by means of gastroscopic observation with pathological biopsy examination. They were divided into 4 types (typeⅠ -Ⅳ ) according to Syndrome Differentiation of traditional Chinese medicine, and each type was subdivided according to treatment into 2 groups, 75 in the PWPC group and 68 in the San jiu Weitai (SJWT, 三九胃泰) group. Patients of PWPC group were in accordance with the type to which they belong treated with PWPC Ⅰ, Ⅱ, Ⅲ, Ⅳ respectively, while patients of SJWT group were all treated with SJWT. After 3 - 6 months of treatment, the clinical effect, pathological examination of gastric mucosa and some other parameters were observed. Results:The improvements of gastric mucosa cyclic adenosing monophosphate (cAMP ), deoxyribonucleic acid (DNA), 3H-thymopyrimidine nucleoside and lymphocyte transformation of the treatment group were all superior to those of SJWT group, P＜ 0. 05 - 0. 001. In the PWPC group, the curative rate and total effective rate on symptom were 49. 3 % and 92. 0% respectively, and the curative rate and total effective rate on intestinal metaplasia were 45. 3 % and 62. 7%. As for the SJWT group, they were 29. 4%, 67. 6%, 10. 3% and 29. 4% respectively. The difference between the two groups was significant, P ＜ 0. 001. Conclusion: PWPC could reverse the intestinal metaplasia through improving the gastric cAMP, DNA and strengthening the cellular immunity and the effect would be enhanced when the treatment was based on Syndrome Differentiation.