Role of pre-existing incomplete intestinal metaplasia in gastric adenocarcinoma:A retrospective case series analysis

BACKGROUND Risk stratification for patients with gastric precancerous lesions for endoscopic surveillance remains controversial.AIM To analysis of patients having developed gastric adenocarcinoma during the period of follow-up.METHODS We conducted a retrospective study on patients having undergone upper endoscopy prior to the development of gastric adenocarcinoma. The presence and stage of precancerous lesions as well as subtype of intestinal metaplasia at the baseline endoscopy got evaluated. Literature mini-review was performed.RESULTS Out of 1681 subjects in the Biobank, gastric adenocarcinoma was detected in five cases in whom previous endoscopy data with biopsies either from the corpus or antral part were available. All of the patients had incomplete intestinal metaplasia during the baseline endoscopy;all three subjects in whom intestinal metaplasia subtyping was performed according to Filipe et al, had Type Ⅲ intestinal metaplasia. Two of the five cases had low Operative Link on Gastritis Assessment(OLGA) and Operative Link on Gastritis Intestinal Metaplasia Assessment(OLGIM) stages(Ⅰ-Ⅱ) at the baseline.CONCLUSION The presence of incomplete intestinal metaplasia, in particular, that of Type Ⅲ is a better predictor for gastric adenocarcinoma development than OLGA/OLGIM staging system. Subtyping of intestinal metaplasia have an important role in the risk stratification for surveillance decisions.

Expression of p53,c-erbB-2 and Ki67 in intestinal metaplasia and gastric carcinoma

AIM:To compare two types of classification of intestinal metaplasia (IM) of the stomach and to explore their relationship to gastric carcinoma.METHODS:Forty-seven cases of gastric IM were classified into type or typeaccordingto mucin histochemical staining and compared with a novel classification in which the specimens were classif ied into simple IM (SIM) or atypical IM according to polymorphism in terms of atypical changes of the metaplastic epithelium. Forty-seven IM and thirty-seven gastric carcinoma samples were stained for p53, c-erbB-2 and Ki67 proteins by Envision immunohistochemical technique.RESULTS: There were no significant differences in the expression of p53 and c-erbB-2 among type type, typeIM and gastric carcinomas. The positive expression rate of Ki67 was significantly higher in gastric carcinomas than in type IM while no signif icant Ki67 expression differences were observed among type,typeIM and gastric carcinomas. The expression ofp53, c-erbB-2 and Ki67 proteins in 20 SIM, 27 Atypical IM and 37 gastric carcinomas showed significant differences between SIM and gastric carcinomas while no significant differences were observed between Atypical IM and gastric carcinomas.CONCLUSION: Atypical IM may better reveal the pre-cancerous nature of IM and could be a helpful indicator in the clinical follow up of patients.

Prevalence and Factors Associated with Intestinal Metaplasia in Chronic Helicobacter pylori Gastritis in a Country with High Endemicity: Ivory Coast Case

Context/Objective: Few studies have been carried out in a country with high endemicity for Helicobacter pylori (H. pylori) infection in Sub-Saharan Africa looking for the association of intestinal metaplasia (IM) with chronic gastritis. We hypothesize that IM is correlated with the intensity of H. pylori infection in a country with high endemicity, Ivory Coast. The objective of this study was to determine the prevalence of intestinal metaplasia in chronic H. pylori gastritis in Ivory Coast. Methods: This was a prospective, cross-sectional, multicenter study, carried out over a period of 5 months, in the reference hospital centers of Abidjan, specialized in Gastroenterology. All patients who had undergone Gastroscopy with biopsies according to the criteria of the Sydney System for the anatomopathological study, those with chronic gastritis and/or H. pylori intestinal metaplasia on histology and in whom all the parameters of the Sydney system classification had been well informed. The quantitative variables were expressed by their means accompanied by their standard deviations and the qualitative variables by their numbers and percentages. Chi-square and Fischer tests were used to look for associations between variables. The significance level was set at 5%. Results: 152 patients were retained. The mean age was 44.9 ± 12.9 years. The prevalence of intestinal metaplasia was 11.8%. In univariate analysis, no significant association was found between clinical and pathological sociodemographic factors (age, sex, ethnicity, educational level, profession) and intestinal metaplasia in chronic Helicobacter pylori gastric cases. In multivariate analysis we found that prolonged use of Proton Pump Inhibitors (PPIs) and a history of Gastroesophageal Reflux Disease (GERD) were significantly associated with the absence of IM. Conclusion: Chronic H. pylori gastritis is the main risk factor for intestinal metaplasia. Prolonged use of PPIs and a history of GERD were significantly identified as factors that would protect against intestinal metaplasia.

BIO-CHARACTERISTICS OF INTESTINAL METAPLASIA IN THE STOMACH: HYPERPROLIFERATIVE AND USUAL TYPE

Background： In Padova and Vienna International Classification, the usual intestinal metaplasia （UIM） of the stomach, including complete and incomplete type, is defined as negative for dysplasia, and hyperproliferative intestinal metaplasia （HIM） as indefinite for dysplasia, but the biological characteristics of these two types of intestinal metaplasia （IM）remain to be studied. Objective： To investigate the biological differences between UIM, HIM and intestinal type gastric cancer （IGC）, a panel of biomarkers were detected. Methods： A total of 38 cases of IGC, 41 HIM and 56 UIM adjacent to gastric cancer were studied. Immunohistochemistry was used to detect the expressions of pS2, MUC2, MUC5AC, MUC6, Ki-67, EGFR, p53 and sulfo-Lewisa in UIM, HIM and IGC. Microsatellite instability （MSI） in UIM, HIM and IGC was detected by using Denaturing High Performance Liquid Chromatography （DHPLC）. Results： The pS2 antigen expression in UIM （78.6%） was significantly higher than in HIM and IGC （9.8%, 10.5%）, p〈0.01. The MUC6, sulfo-Lewisa and EGFR protein expressions were significant increased in HIM （24.4%, 82.9%, 48.7%） and IGC （34.2%, 75.0%, 42.1%） than in UIM （3.6%, 25.5%, 17.9%）, p〈0.01. A reversed pattern of expressions of MUC2 and MUC5AC was observed in UIM （96.4%, 50.0%） and HIM （82.9%, 36.6%） compared with IGC （52.6%, 13.2%）, p〈0.05; and the p53 gene expression was increased from UIM （1.8%） to HIM （19.5%） to IGC （57.9%）, p〈0.01. The Ki-67 labeling index was significantiy different among three lesions （UIM： 16%±6%, HIM： 45%±9%, IGC： 63%±10%, p〈0.01）. Conclusion： These findings suggest that there are different bio-characteristics among UIM, HIM and IGC, and HIM may have higher potential to progress to more advanced lesions in comparison with UIM.

Operative link for gastritis assessment vs operative link on intestinal metaplasia assessment

AIM:To compare the reliability of gastritis staging sys-tems in ranking gastritis-associated cancer risk in a large series of consecutive patients.METHODS:Gastric mucosal atrophy is the precancer-ous condition in which intestinal-type gastric cancer(GC)most frequently develops.The operative link for gas-tritis assessment(OLGA)staging system ranks the GC risk according to both the topography and the severity of gastric atrophy(as assessed histologically on the ba-sis of the Sydney protocol for gastric mucosal biopsy).Both cross-sectional and long-term follow-up trials have consistently associated OLGA stages Ⅲ-Ⅳ with a higher risk of GC.A recently-proposed modification of the OLGA staging system(OLGIM)basically incorporates the OLGA frame,but replaces the atrophy score with an assessment of intestinal metaplasia(IM)alone.A series of 4552 consecutive biopsy sets(2007-2009)was re-trieved and reassessed according to both the OLGA and the OLGIM staging systems.A set of at least 5 biopsy samples was available for all the cases considered.RESULTS:In 4460 of 4552 cases(98.0%),both the high-risk stages(Ⅲ + Ⅳ)and the low-risk stages(0 +Ⅰ + Ⅱ)were assessed applying the OLGA and OL-GIM criteria.Among the 243 OLGA high-risk stages,14(5.8%)were down-staged to a low risk using OLGIM.The 67(1.5%)incidentally-found neoplastic lesions(intraepithelial or invasive)were consistently associated with high-risk stages,as assessed by both OLGA and OLGIM(P < 0.001 for both).Two of 34 intestinal-type GCs coexisting with a high-risk OLGA stage(stage Ⅲ)were associated with a low-risk OLGIM stage(stage Ⅱ).CONCLUSION:Gastritis staging systems(both OLGA and OLGIM)convey prognostically important informa-tion on the gastritis-associated cancer risk.Because of its clinical impact,the stage of gastritis should be included as a conclusive message in the gastritis histol-ogy report.Since it focuses on IM alone,OLGIM staging is less sensitive than OLGA staging in the identif ication of patients at high risk of gastric cancer.

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.

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.

Expression of COX-2 in Different Subtypes of Gastric Intestinal Metaplasia and Gastric Carcinoma by Tissue Microarray

Objective: To study the expression of cyclooxygenase-2 (COX-2) protein in different subtypes of intestinal metaplasia (IM) and gastric carcinoma, evaluate the possibility of COX-2 forecasting the risk of malignant potential of IM, and the relationship between COX-2 expression and gastric carcinogenesis. Methods: Forty cases of chronic atrophic gastritis (CAG) with IM, 40 cases of gastric carcinoma and corresponding paracancerous tissues were selected to construct a tissue microarray. High iron diamine/alcian blue (HID/AB) staining and Hematoxylin and Eosin (HE) staining was used to classify IM and gastric carcinoma, and the expression of COX-2 protein detected in different subtypes of IM and gastric cancer by using immunohistochemistry. Results: The positive expression rate of COX-2 was 45.65%, 59.38% and 77.27% in IM foci in CAG, IM foci in paracancerous tissues, and intestinal-type gastric carcinoma, respectively, significantly higher than in diffuse-type gastric cancer (16.67%)(P<0.05, 0.005 and 0.005, respectively), and the expression intensity of COX-2 protein showed a increased tendency gradually in the sequence of IM foci in CAG→IM foci in paracancerous tissues→intestinal-type gastric carcinoma (P<0.005). The positive expression rate of COX-2 protein in type Ⅲ IM was significantly higher than in type Ⅰ and type Ⅱ IM (P<0.005 and 0.05, respectively), and the expression intensity also showed a increased tendency gradually from type Ⅰ to type Ⅲ IM (P<0.005). Conclusion: The expression level of COX-2 was increased gradually along with the increase of the risk of malignancy of IM, and its expression level may be a useful index to forecast the risk of malignant potential of IM. COX-2 expression was associated with intestinal-type gastric carcinoma, but it might also have some role in the carcinogenesis of diffuse-type gastric carcinoma.

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.

Difference of Gene Expression Profiles between Barrett’s Esophagus and Cardia Intestinal Metaplasia by Gene Chip

The difference of gene expression profile changes in Barrett＇s esophagus （BE） and cardia intestinal metaplasia （CIM） epithelium was studied and the novel associated genes were screened in the early stage by cDNA microarray. The cDNA retro-transcribed from equal quantity mRNA from BE and CIM epithelial tissues were labeled with Cy3 and Cy5 fluorescence as probes. The mixed probe was hybridized with three pieces BiostarH-40s double dot human whole gene chip. The chips were scanned with a ScanArray 4000. The acquired images were analyzed using GenePix Pro 3.0 software. It was found a total of 141 genes were screened out that exhibited differentially expression more than 2 times in all three chips. It was identified that in gene expression profiles of BE, 74 genes were up-regulated and 67 down-regulated as compared with CIM. The comparison between the difference of gene expression profile changes in BE and CIM epithelia revealed that there existed the difference between BE and CIM at gene level. 141 genes with the expression more than two time were probably related to the occurrence and development of BE and the promotion or progress in adenocarcinoma.

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.

Follow-up of intestinal metaplasia in the stomach: When, how and why

Gastric cancer remains the second most frequent cause of cancer-related mortality in the world. Screening programs in some Asian countries are impractical in the majority of other countries worldwide. Therefore, follow-up of precancerous lesions is advisable for secondary gastric cancer prevention. Intestinal metaplasia (IM) is recognized as a precancerous lesion for gastric cancer, increasing the risk by 6-fold. IM is highly prevalent in the general population, being detected in nearly 1 of every 4 patients undergoing upper endoscopy. The IM prevalence rate is significantly higher in patients with Helicobacter pylori (H. pylori) infection, in first-degree relatives of gastric cancer patients, in smokers and it increases with patient age. IM is the "breaking point" in the gastric carcinogenesis cascade and does not appear to regress following H. pylori eradication, although the cure of infection may slow its progression. Gastric cancer risk is higher in patients with incomplete-type IM, in those with both antral and gastric body involvement, and the risk significantly increases with IM extension over 20% of the gastric mucosa. Scheduled endoscopic control could be cost-effective in IM patients, depending on the yearly incidence of gastric cancer in IM patients, the stage of gastric cancer at diagnosis discovered at surveillance, and the cost of endoscopy. As a pragmatic behavior, yearly endoscopic control would appear justified in all IM patients with at least one of these conditions: (1) IM extension > 20%; (2) the presence of incomplete type IM; (3) first-degree relative of gastric cancer patients; and (4) smokers. In the remaining IM patients, a less intensive (2-3 years) could be proposed.

Narrow-band imaging with magnifying endoscopy is accurate for detecting gastric intestinal metaplasia

AIM:To investigate the predictive value of narrowband imaging with magnifying endoscopy (NBI-ME) for identifying gastric intestinal metaplasia (GIM) in unselected patients. METHODS:We prospectively evaluated consecutive patients undergoing upper endoscopy for various indications, such as epigastric discomfort/pain, anaemia, gastro-oesophageal reflux disease, suspicion of peptic ulcer disease, or chronic liver diseases. Patients underwent NBI-ME, which was performed by three blinded, experienced endoscopists. In addition, five biopsies (2 antrum, 1 angulus, and 2 corpus) were taken and examined by two pathologists unaware of the endoscopic findings to determine the presence or absence of GIM. The correlation between light blue crest (LBC) appearance and histology was measured. Moreover, we quantified the degree of LBC appearance as less than 20% (+), 20%-80% (++) and more than 80% (+++) of an image field, and the semiquantitative evaluation of LBC appearance was correlated with IM percentage from the histological findings. RESULTS:We enrolled 100 (58 F/42 M) patients who were mainly referred for gastro-esophageal reflux disease/dyspepsia (46%), cancer screening/anaemia (34%), chronic liver disease (9%), and suspected celiac disease (6%); the remaining patients were referred for other indications. The prevalence of Helicobacter pylori (H. pylori ) infection detected from the biopsies was 31%, while 67% of the patients used proton pump inhibitors. LBCs were found in the antrum of 33 patients (33%); 20 of the cases were classified as LBC+, 9 as LBC++, and 4 as LBC+++. LBCs were found in the gastric body of 6 patients (6%), with 5 of them also having LBCs in the antrum. The correlation between the appearance of LBCs and histological GIM was good, with a sensitivity of 80% (95%CI:67-92), a specificity of 96% (95%CI:93-99), a positive predictive value of 84% (95%CI:73-96), a negative predictive value of 95% (95%CI:92-98), and an accuracy of 93% (95%CI:90-97). The NBI-ME examination overlooked GIM in 8 cases, but the GIM was less than 5% in 7 of the cases. Moreover, in the 6 false positive cases, the histological examination showed the presence of reactive gastropathy (4 cases) or H. pylori active chronic gastritis (2 cases). The semiquantitative correlation between the rate of LBC appearance and the percentage of GIM was 79% (P < 0.01). CONCLUSION:NBI-ME achieved good sensitivity and specificity in recognising GIM in an unselected population. In routine clinical practice, this technique can reliably target gastric biopsies.

Inflammatory cytokine gene polymorphisms increase the risk of atrophic gastritis and intestinal metaplasia

AIM: To investigate the effects of interleukin-8 (IL-8 ), macrophage migration inhibitory factor (MIF ) gene polymorphisms, Helicobacter pylori (H. pylori ) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM). METHODS: A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progres-sion group (no histological progression from normal or superficial gastritis, n = 137), group Ⅰ (progressed from normal or superficial gastritis to SCAG, n = 134) and group Ⅱ (progressed from normal or superficial gastritis to IM, n = 101). IL-8 , MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing. RESULTS: An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection. CONCLUSION: IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.

Helicobacter pylori infection, glandular atrophy and intestinal metaplasia in superficial gastritis, gastric erosion, erosive gastritis, gastric ulcer and early gastric cancer

AIM: To evaluate the histological features of gastric mucosa, including Helicobacter pylori infection in patients with early gastric cancer and endoscopically found superficial gastritis, gastric erosion, erosive gastritis, gastric ulcer. METHODS: The biopsy specimens were taken from the antrum, corpus and upper angulus of all the patients. Giemsa staining, improved toluidine-blue staining, and Hpylori-specific antibody immune staining were performed as appropriate for the histological diagnosis of H pylori infection. Hematoxylin-eosin staining was used for the histological diagnosis of gastric mucosa inflammation, gastric glandular atrophy and intestinal metaplasia and scored into four grades according to the Updated Sydney System. RESULTS: The overall prevalence of H pylori infection in superficial gastritis was 28.7%, in erosive gastritis 57.7%, in gastric erosion 63.3%, in gastric ulcer 80.8%, in early gastric cancer 52.4%. There was significant difference (P<0.05), except for the difference between early gastric cancer and erosive gastritis. H pylori infection rate in antrum, corpus, angulus of patients with superficial gastritis was 25.9%, 26.2%, 25.2%, respectively; in patients with erosive gastritis 46.9%, 53.5%, 49.0%, respectively; in patients with gastric erosion 52.4%, 61.5%, 52.4%, respectively; in patients with gastric ulcer 52.4%, 61.5%, 52.4%, respectively; in patients with early gastric cancer 35.0%, 50.7%, 34.6%, respectively. No significant difference was found among the different site biopsies in superficial gastritis, but in the other diseases the detected rates were higher in corpus biopsy (P<0.05). The grades of mononuclear cell infiltration and polymorphonuclear cell infiltration, in early gastric cancer patients, were significantly higher than that in superficial gastritis patients, lower than that in gastric erosion and gastric ulcer patients (P<0.01); however, there was no significant difference compared with erosive gastritis. The grades of mucosa glandular atrophy and intestinal metaplasia were significantly highest in early gastric cancer, lower in gastric ulcer, the next were erosive gastritis, gastric erosion, the lowest in superficial gastritis (P<0.01). Furthermore, 53.3% and 51.4% showed glandular atrophy and intestinal metaplasia in angular biopsy specimens, respectively; but only 40.3% and 39.9% were identified in antral biopsy, and 14.1% and 13.6% in corpus biopsy; therefore, the angulus was more reliable for the diagnosis of glandular atrophy and intestinal metaplasia compared with antrum and corpus (P<0.01). The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis with H pyloripositivity was 50.7%, 34.1%; of erosive gastritis 76.1%, 63.0%; of gastric erosion 84.8%, 87.8%; of gastric ulcer 80.6%, 90.9%; and of early gastric cancer 85.5%, 85.3%, respectively. The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis with H pylorinegativity was 9.9%, 6.9%; of erosive gastritis 42.5%, 42.1%; of gastric erosion 51.1%, 61.9%; of gastric ulcer 29.8%, 25.5%; and of early gastric cancer 84.0%, 86.0%, respectively. The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis, erosive gastritis, gastric erosion, and gastric ulcer patients with H pylon positivity was significantly higher than those with H pylori negativity (P<0.01); however, there was no significant difference in patients with early gastric cancer with or without H pylori infection. CONCLUSION: The progression of the gastric pre-cancerous lesions, glandular atrophy and intestinal metaplasia in superficial gastritis, gastric erosion, erosive gastritis and gastric ulcer was strongly related to H pylori infection. In depth studies are needed to evaluate whether eradication of H pylori infection will really diminish the risk of gastric cancer.

-765G > C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia

AIM： To investigate the relationship between the -765G 〉 C COX-2 polymorphism and the development of different gastric lesions： atrophy or intestinal metaplasia and gastric adenocarcinoma. METHODS： A cross-sectional study was performed involving 320 Portuguese individuals （210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia） using a PCR-RFLP method.RESULTS： -765C allele was overrepresented in the patients with gastric adenocarcinoma （51%） when compared either with the control group （38%） or patients with atrophy or intestinal metaplasia （27%）. Callele was found to be very common in our population （0.22）, and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele （OR = 2.67, 95% CI = 1.03-6.93; P = 0.04）.CONCLUSION： -765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.

Role of digital chromoendoscopy and confocal laser endomicroscopy for gastric intestinal metaplasia and cancer surveillance

In Japan and countries such as South Korea and Tai-wan, China, the standard technique for detecting earlygastric cancer (EGC) is chromoendoscopy. This technique involves a magnified endoscope and the use ofan indigo-carmine spray to distinguish between EGCand non-EGC areas. However, this technique is notwidely adopted in many parts of the world. One important reason for limited use is that this technique needsan experienced endoscopist to interpret the imagesduring the procedure. In addition, the sensitivity for detecting gastric intestinal metaplasia (GIM), a precancerous lesion of EGC, is graded as suboptimal. Moreover,the requirement of a cumbersome spraying method isinconvenient and needs preparation time. Easier digitalchromoendoscopy techniques, such as Narrow-bandImaging and Flexible spectral Imaging Color Enhancement, have been reported to facilitate targeted GIM and EGC biopsy. They provide higher sensitivities over conventional white light endoscopy. Recently, the noveltechnology of confocal laser endomicroscopy has been introduced as a high-magnification (1000 ×) real-time evaluation for many early gastrointestinal (GI) cancersand precancerous GI lesions, including colonic polyp,Barrett's esophagus, and GIM. The advantage of this technique is that it can be used as an in vivo confirmation of the presence of GIM and EGC during endoscopic surveillance. This review aims to explain the current information on the usefulness of digital chromoendos-copy and confocal laser endomicroscopy for evaluating GIM and EGC during endoscopic surveillance and the possible future role of these techniques for GI cancerscreening programs.

Short-segment Barrett's esophagus and cardia intestinal metaplasia:A comparative analysis

AIM:To investigate the endoscopy and histology of short-segment Barrett's esophagus (SSBE) and cardia intestinal metaplasia (CIM),and their correlation with Helicobacter pylori (H. pylori) gastritis and gastroesophageal reflux disease (GERD). METHODS:Biopsy specimens were taken from 32 SSBE patients and 41 CIM patients with normal appearance of the esophagogastric junction. Eight biopsy specimens from the lower esophagus,cardia,and gastric antrum were stained with hematoxylin/eosin,Alcian blue/periodic acid-Schiff,Alcian blue/high iron diamine and Gimenez dye. Results were graded independently by one pathologist. RESULTS:The SSBE patients were younger than the CIM patients (P < 0.01). The incidence of dysplasia and incomplete intestinal metaplasia subtype was higher in SSBE patients than in CIM patients (P < 0.01). H. pylori infection was correlated with antral intestinal metaplasia (P < 0.05),but not with reflux symptomatic,endoscopic,or histological markers of GERD in CIM patients. SSBE was correlated with reflux symptomatic and endoscopic esophagitis (P < 0.01),but not with H. pylori infection and antral intestinal metaplasia. CONCLUSION:Dysplasia risk is significantly greater in SSBE patients than in CIM patients. CIM is a manifestation of H. pylori-associated and multifocal atrophic gastritis,whereas SSBE may result from GERD.