Helicobacter pylori plays a key role in gastric adenocarcinoma induced by spasmolytic polypeptide-expressing metaplasia

Heliobacter pylori(H. pylori), a group 1 human gastric carcinogen, is significantly associated with chronic gastritis, gastric mucosal atrophy, and gastric cancer.Approximately 20% of patients infected with H. pylori develop precancerous lesions, among which metaplasia is the most critical. Except for intestinal metaplasia(IM), which is characterized by goblet cells appearing in the stomach glands, one type of mucous cell metaplasia, spasmolytic polypeptide-expressing metaplasia(SPEM), has attracted much attention. Epidemiological and clinicopathological studies suggest that SPEM may be more strongly linked to gastric adenocarcinoma than IM. SPEM, characterized by abnormal expression of trefoil factor 2, mucin 6, and Griffonia simplicifolia lectin II in the deep glands of the stomach, is caused by acute injury or inflammation. Although it is generally believed that the loss of parietal cells alone is a sufficient and direct cause of SPEM, further in-depth studies have revealed the critical role of immunosignals.There is controversy regarding whether SPEM cells originate from the transdifferentiation of mature chief cells or professional progenitors. SPEM plays a functional role in the repair of gastric epithelial injury. However, chronic inflammation and immune responses caused by H. pylori infection can induce further progression of SPEM to IM, dysplasia, and adenocarcinoma. SPEM cells upregulate the expression of whey acidic protein 4-disulfide core domain protein 2 and CD44 variant 9, which recruit M2 macrophages to the wound. Studies have revealed that interleukin-33, the most significantly upregulated cytokine in macrophages, promotes SPEM toward more advanced metaplasia. Overall, more effort is needed to reveal the specific mechanism of SPEM malignant progression driven by H.pylori infection.

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.

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.

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.

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.

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.

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.

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.

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.

Cdx2 expression and its promoter methylation during metaplasia-dysplasia-carcinoma sequence in Barrett's esophagus

AIM:To examine how the expression of caudal type homebox transcription factor 2(Cdx2) is regulated in the development of malignancy in Barrett's esophagus.METHODS:Cdx2,mucin(MUC) series(MUC2,MUC5AC and MUC6),p53 and E-cadherin expression in Barrett's esophagus and adenocarcinoma specimens were examined by immunostaining.Isolated clusters of cells from(1) MUC2 and Cdx2-positive intestinal metaplastic mucosa;(2) MUC5AC and MUC6-positive,and MUC2 and Cdx2-negative high-grade dysplasia(HD),or intramucosal adenocarcinoma(IMC);and(3) MUC5AC,MUC6 and Cdx2-positive poorly-differentiated invasive adenocarcinoma(PDA) were analyzed by methylationspecific polymerase chain reaction using sets of primers for detecting methylation status of the Cdx2 gene.RESULTS:Most of the non-neoplastic Barrett's esophageal mucosa showing intestinal-type metaplasia with or without low-grade dysplasia was positive for E-cadherin,MUC series and Cdx2,but negative for p53.A portion of the low-grade to HD was positive for E-cadherin,MUC5AC,MUC6 and p53,but negative for MUC2 and Cdx2.The definite IMC area was strongly positive for MUC5AC,MUC6 and p53,but negative for MUC2 and Cdx2.Methylation of the Cdx2 promoter was not observed in intestinal metaplasia,while hypermethylation of part of its promoter was observed in hot dipped and IMC.Hypermethylation of a large fraction of the Cdx2 promoter was observed in PDA.CONCLUSION:Cdx2 expression is restored irrespective of the methylation status of its promoter.Apparent positive immunohistochemical results can be a molecular mark for gene silencing memory.

Helicobacter pylori associated gastric intestinal metaplasia:Treatment and surveillance

Gastric cancer(GC) is one of the leading causes of cancer related death in the world, particularly in East Asia. According to the Correa's cancer cascade, noncardia GC is usually developed through a series of mucosal changes from non-atrophic gastritis to atrophic gastritis(AG), intestinal metaplasia(IM), dysplasia and adenocarcinoma. Atrophic gastritis and IM are therefore generally considered to be pre-neoplastic gastric lesions. Helicobacter pylori(H. pylori) infection is an important initiating and promoting step of this gastric carcinogenesis cascade. Emerging long-term data showed that eradication of H. pylori reduced the risk of subsequent cancer development. It however remains confusing whether eradication of the bacterium in individuals with pre-neoplastic gastric lesions could regress these changes as well as in preventing cancer. Whilst H. pylori eradication could likely regress AG, the presence of IM may be a point of no return in this cascade. Hence, surveillance by endoscopy may be indicated in those with extensive IM or those with incomplete IM, particularly in populations with high GC risk. The optimal interval and the best tool of surveillance endoscopy remains to be determined in future studies.

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.

Intestinal metaplasia surveillance:Searching for the roadmap

Atrophic gastritis and intestinal metaplasia(IM) of the stomach are common and are associated with an increased risk for gastric cancer.In the absence of guidelines,a pragmatic management has been performed in Western countries in patients with these premalignant conditions.Recently,formal European guidelines have been delivered on this topic.Basically,it has been recommended that patients with extensive atrophic gastritis(AG) and/or extensive IM should be offered endoscopic surveillance every 3 years.On the contrary,no scheduled endoscopic/histological control has been advised for those patients with precancerous conditions confined to the antrum.In this commentary,we highlighted some potential weaknesses in the management formally recommended by the new guidelines.In detail,we discussed that AG and IM patients do not share the same gastric cancer risk,at least in Western countries,deserving a different approach.Some factors significantly associated with gastric cancer risk,such as IM type,first-degree family history of gastric cancer,and smoking habit have not been considered in tailoring the endoscopic follow-up.Finally,some data would suggest that a 3-year follow-up in patients with extensive gastric precancerous conditions could result in an inadequate secondary prevention.

Effect of medical and surgical treatment of Barrett's metaplasia

Barrett’s esophagus (BE) is a change in the esophageal mucosa as a result of long-standing gastroesophageal reflux disease. The importance of BE is that it is the main risk factor for the development of esophageal adenocarcinoma, whose incidence is currently growing faster than any other cancer in the Western world. The aim of this review was to compare the common treatment modalities of BE, with the focus on proton pump inhibitors and operative fundoplication. We performed a literature search on medical and surgical treatment of BE to determine eligible studies for this review. Studies on medical and surgical treatment of BE are discussed with regard to treatment effect on progression and regression of disease. Although there is some evidence for control of reflux with either medical or surgical therapy, there is no def initive evidence that either treatment modality decreases the risk of progression to dysplasia or cancer. Even though there is a trend toward antireflux surgery being superior, there are no def initive studies to prove this.

Methylation of DAPK and THBS1 genes in esophageal gastric-type columnar metaplasia

AIM: To explore methylation of DAPK, THBS1, CDH-1, and p14 genes, and Helicobacter pylori(H. pylori) status in individuals harboring esophageal columnar metaplasia.METHODS: Distal esophageal mucosal samples obtained by endoscopy and histologically diagnosed as gastric-type(non-specialized) columnar metaplasia, were studied thoroughly. DNA was extracted from paraffin blocks, and methylation status of deathassociated protein kinase(DAPK), thrombospondin-1(THBS1), cadherin-1(CDH1), and p14 genes, was examined using a methyl-sensitive polymerase chain reaction(MS-PCR) and sodium bisulfite modification protocol. H. pylori cag A status was determined by PCR.RESULTS: In total, 68 subjects(33 females and 35 males), with a mean age of 52 years, were included. H. pylori cag A positive was present in the esophageal gastric-type metaplastic mucosa of 18 individuals. DAPK, THSB1, CDH1, and p14 gene promoters were methylated by MS-PCR in 40(58.8%), 33(48.5%), 46(67.6%), and 23(33.8%) cases of the 68 esophageal samples. H. pyloristatus was associated with methylation of DAPK(P = 0.003) and THBS1(P = 0.019).CONCLUSION: DNA methylation occurs in cases of gastric-type(non-specialized) columnar metaplasia of the esophagus, and this modification is associated with H. pylori cag A positive infection.

Evaluation of the Gastric Microbiome in Patients with Chronic Superficial Gastritis and Intestinal Metaplasia

Objective To evaluate the gastric microbiome in patients with chronic superficial gastritis(CSG)and intestinal metaplasia(IM)and investigate the influence of Helicobacter pylori(H.pylori)on the gastric microbiome.Methods Gastric mucosa tissue samples were collected from 54 patients with CSG and IM,and the patients were classified into the following four groups based on the state of H.pylori infection and histology:H.pylori-negative CSG(n=24),H.pylori-positive CSG(n=14),H.pylori-negative IM(n=11),and H.pylori-positive IM(n=5).The gastric microbiome was analyzed by 16S rRNA gene sequencing.Results H.pylori strongly influenced the bacterial abundance and diversity regardless of CSG and IM.In H.pylori-positive subjects,the bacterial abundance and diversity were significantly lower than in H.pylori-negative subjects.The H.pylori-negative groups had similar bacterial composition and bacterial abundance.The H.pylori-positive groups also had similar bacterial composition but different bacterial relative abundance.The relative abundance of Neisseria,Streptococcus,Rothia,and Veillonella were richer in the I-HP group than in G-HP group,especially Neisseria(t=175.1,P<0.001).Conclusions The gastric microbial abundance and diversity are lower in H.pylori-infected patients regardless of CSG and IM.Compared to H.pylori-positive CSG group and H.pylori-positive IM,the relative abundance of Neisseria,Streptococcus,Rothia,and Veillonella is higher in H.pylori-positive patients with IM than in H.pylori-positive patients with CSG,especially Neisseria.

Preventive and inhibitive effects of Yiwei Xiaoyu granules on the development and progression of spasmolytic polypeptideexpressing metaplasia lesions

BACKGROUND Spasmolytic polypeptide-expressing metaplasia(SPEM)is a potential preneoplastic lesion.AIM To elucidate the microRNA(miR)-7-mediated preventive and inhibitive effects of Yiwei Xiaoyu granules(YWXY)in SPEM lesions.METHODS Gastric mucosa biopsies were collected from chronic atrophic gastritis patients and healthy people with signed informed consent.YWXY was administered to the mice with induced SPEM by tamoxifen,and the gastric mucosa was harvested on the tenth day of the experiment.Then immunohistochemistry and immunofluorescence were performed to validate the SPEM,lesions and the potential mechanism was investigated.RNA transcripts were detected with reverse transcriptionquantitative polymerase chain reaction.RESULTS The expression of miR-7 was downregulated in the SPEM lesions,and expression of trefoil factor 2(TFF2)and clusterin was high in the human gastric mucosa.In vivo experiments showed that YWXY could inhibit the cell proliferation in the tamoxifen-induced SPEM lesions by regulating Ki67.Simultaneously,YWXY could restore the expression of miR-7 by regulating TFF2 by detection with immunofluorescence but not with reverse transcription-quantitative polymerase chain reaction,indicating its potential mechanism of targeting miR-7 by mediating TFF2.The expression of vascular endothelial growth factor-βand gastric intrinsic factor was restored within 3 d of YWXY administration for the SPEM lesions,speculating that the possible mechanism of YWXY is to inhibit the development and progression of SPEM by regulating vascular endothelial growth factor-βand gastric intrinsic factor.CONCLUSION miR-7 downregulation is an early event in SPEM through regulation of TFF2 in human gastric mucosa.YWXY is able to inhibit the cell proliferation and restore the expression of miR-7 by mediating TFF2 in the SPEM mouse model.

Long-term Follow-up Study on Gastric Intestinal Metaplasia Subtype and Its Relation to Expression of P53,Bcl-2 and PCNA

Objective： To investigate the correlation of typies of gastric intestinal metaplasia（IM）, expression of p53, bcl-2 and the proliferating cell nuclear antigen（PCNA）, with the lesion＇s evolution. Methods： A total of 80 patients with IM（53 male and 27 female, 35-64 years old） from an area with high-risk of gastric cancer（GC） in China were enrolled into this prospective study, including 28 cases of type Ⅰ （complete）, 25 cases of type Ⅱ （incomplete） , and 27 cases of type Ⅲ （incomplete）. Of the 80 cases, 62 cases including 19 cases of type Ⅰ, 22 type Ⅱ and 21 type Ⅲ, were followed up for 5-14 years（49 cases for 14 years, 6 for 10 years, and 7 for 5 years）. All of the 80 cases were studied immunohistochemically for the expression of p53, bcl-2 and PCNA. Results： The rate of p53-expressing cases was higher in type Ⅲ（25.9%） than in type Ⅰ（10.7%） and type Ⅱ （12.0%）, but without statistical significance（P=0.3070）. The positive rate of bcl-2 was obviously lower in type Ⅰ （21.4%） and type Ⅱ （24.0%） than in type Ⅲ（37.0%）, but not statistically significant（P=0.4223）. We observed difference in PCNA labelling index （LI） between type Ⅱ and type Ⅲ（P=0.0037）, and the difference was particularly significant in type Ⅰ as compared with type Ⅲ（P〈0.0001）. There was no statistical significance between type I and type II （P=0.0616）. Evolution into GC was detected in 0%, 4.5%, and 14.3% of type Ⅰ, type Ⅱ, and type Ⅲ IM cases, respectively. Progression to dysplasia was detected in 31.6%, 18.2%, and 14.3% of type Ⅰ, type Ⅱ, and type Ⅲ IM cases, respectively. Persistence of IM was documented in 31.6%, 45.5%, and 42.9% of type Ⅰ, type Ⅱ, and type Ⅲ IM cases, respectively. Regression of IM was documented in 36.8%, 31.8%, and 28.6% of type Ⅰ, type Ⅱ, and type ⅢIM cases, respectively. In progressive, persistent and regressive groups, the positive rates of p53 were 17.6%, 16.0% and 15.0%, bcl-2 were 29.4%, 36.0% and 25.0%, and PCNA LIs were 24.953±14.477, 23.752±12.934 and 25.105±10.055, respectively. There were no significant differences between the groups. Conclusion： The present follow-up study indicated that type Ⅲ had a higher risk for development of cancer than type Ⅰ or Ⅱ. PCNA LI was significantly higher in type Ⅲthan in type Ⅰ and Ⅱ, suggesting that cell proliferation in type Ⅲwas more active. Our data also indicated that the expression of p53 and bcl-2 had no apparent association with the particular type and the expression of p53, bcl-2 and PCNA had no apparent correlation with evolution of IM. Further studies with a larger sample size are needed to verify present observation.