Successful Helicobacter Pylori Eradication Research Articles

Early-Stage Gastric Cancer Can Be Found in Improved Atrophic Mucosa over Time from Successful Helicobacter pylori Eradication

Background/Aims: Early-stage gastric cancer (EGC) is detected even after successful Helicobacter pylori eradication. This study is aimed at clarifying the clinicopathological characteristics of EGC detected after successful H. pylori eradication. Methods: This retrospective study analyzed 57 cases of EGC detected after successful H. pylori eradication and resected endoscopically at Kyoto Prefectural University of Medicine, between January 2009 and June 2014. Clinicopathological findings of 57 cases (H. pylori-eradicated group) were investigated, and compared with those in active H. pylori infection resected in the same period (H. pylori-positive group). Results: Most EGCs were detected in patients with severe atrophic mucosa, both in H. pylori-eradicated and H. pylori-positive groups, while the percentage of EGC detected in patients with mild atrophic mucosa gradually increased over time from successful eradication (H. pylori-positive: 7%, up to the fourth year since eradication: 11%, after the fifth year since eradication: 32%). The percentage of EGC detected in patients with mild atrophic mucosa after the fifth year since eradication was significantly higher than that in patients with active H. pylori infection (p = 0.004). Conclusion: After the fifth year following eradication, we should be alert to the incidence of EGC, irrespective of the severity of mucosal atrophic change.

The B-cell-activating factor signalling pathway is associated with Helicobacter pylori independence in gastric mucosa-associated lymphoid tissue lymphoma without t(11;18)(q21;q21).

We previously reported that activation of the B-cell-activating factor (BAFF) pathway upregulates nuclear factor-κB (NF-κB) and induces BCL3 and BCL10 nuclear translocation in Helicobacter pylori (HP)-independent gastric diffuse large B-cell lymphoma (DLBCL) tumours with evidence of mucosa-associated lymphoid tissue (MALT). However, the significance of BAFF expression in HP independence of gastric low-grade MALT lymphomas without t(11;18)(q21;q21) remains unexplored. Sixty-four patients who underwent successful HP eradication for localized HP-positive gastric MALT lymphomas without t(11;18)(q21;q21) were studied. BAFF expression was significantly higher in the HP-independent group than in the HP-dependent group [22/26 (84.6%) versus 8/38 (21.1%); p < 0.001]. Similarly, BAFF receptor (BAFF-R) expression (p = 0.004) and nuclear BCL3 (p = 0.004), BCL10 (p < 0.001), NF-κB (p65) (p = 0.001) and NF-κB (p52) (p = 0.005) expression were closely correlated with the HP independence of these tumours. Moreover, BAFF overexpression was significantly associated with BAFF-R expression and nuclear BCL3, BCL10, NF-κB (p65) and NF-κB (p52) expression. These findings were further validated in an independent cohort, including 40 HP-dependent cases and 18 HP-independent cases of gastric MALT lymphoma without t(11;18)(q21;q21). The biological significance of BAFF signalling in t(11;18)(q21;q21)-negative lymphoma cells was further studied in two types of lymphoma B cell: OCI-Ly3 [non-germinal centre B-cell origin DLBCL without t(11;18)(q21;q21) cell line] and MA-1 [t(14;18)(q32;q21)/IGH-MALT1-positive DLBCL cell line]. In both cell lines, we found that BAFF activated the canonical NF-κB and AKT pathways, and induced the formation of BCL10-BCL3 complexes, which translocated to the nucleus. BCL10 and BCL3 nuclear translocation and NF-κB (p65) transactivation were inhibited by either LY294002 or by silencing BCL3 or BCL10 with small interfering RNA. BAFF also activated non-canonical NF-κB pathways (p52) through tumour necrosis factor receptor-associated factor 3 degradation, NF-κB-inducing kinase accumulation, inhibitor of κB kinase (IKK) α/β phosphorylation and NF-κB p100 processing in both cell lines. Our data indicate that the autocrine BAFF signal transduction pathway contributes to HP independence in gastric MALT lymphomas without the t(11;18)(q21;q21) translocation. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Usefulness of Endoscopic Findings for Predicting the Risk of Gastric Cancer after Eradication of Helicobacter pylori

Introduction:Helicobacter pylori (HP) is one of important risk factors for gastric cancer. Even after eradication of HP, however, gastric cancer develops in some cases. Endoscopic examination is useful for not only evaluating the severity of gastritis but also screening gastric cancer. Therefore, it is very important to evaluate whether or not endoscopic findings could predict the risk of gastric cancer after eradicating HP. Methods: 42 patients, in whom HP was eradicated from July 2007 to October 2013 and esophago-gastroduodenal endoscopy was performed before and 1, 2 and 3 years after eradicating HP, were enrolled retrospectively. The difference of endoscopic findings was evaluated between the two groups; the cancer group in which gastric cancer developed after eradicating HP, and the non-cancer group. Results: Of 42 patients, 26 were male, and the median age was 65 years (range 35-82 years). Before eradicating HP, the number of patients based on Kimura and Takemoto classification of atrophic gastritis was as follows; C-1 n=4/C-2 n=2/C-3 n=2 /O-1 n=11/ O-2 n=16/O-3 n=7. After eradication of HP, gastric cancers developed in ten patients (23.8 %). Comparing the difference of clinical characteristics between the cancer group and the non-cancer one, the number of patients with severe atrophic gastritis, such as O-2 and O-3, before eradicating HP was significantly greater in the cancer group than that in the noncancer group (p-value<0.05). Even after eradicating HP, moreover, the rate of severe atrophic gastritis in the cancer group was significantly higher than that in the non-cancer group (p-value<0.05).Three years after eradicating HP, particularly, the frequencies of RAC and intestinal metaplasia in the cancer group were less and higher than those in the non-cancer group, respectively (p-value<0.05). Conclusion: Commonly, eradicating HP improves not only the endoscopic findings of atrophic gastritis but also the risk for gastric cancer. However, our data demonstrated the risk for gastric cancer remained still high in patients with severe atrophic gastritis despite eradicating HP.SymbolTherefore, severe atrophic endoscopic-findings after eradicating HP would be useful for predicting the risk of gastric cancer. In conclusion, for the patients with severe atrophic gastritis even after successful eradication of HP, our gastroenterologists should pay attention for the possibility of gastric cancer.Symbol

Mo1356 The Endoscopic Features of Early Gastric Cancer After Successful Eradication of Helicobacter pylori

Mo1356 The Endoscopic Features of Early Gastric Cancer After Successful Eradication of Helicobacter pylori

Upregulation of Vanilloid Receptor-1 in Functional Dyspepsia With or Without Helicobacter pylori Infection.

The etiological basis of functional dyspepsia (FD) is incompletely understood. The aim of this study was to evaluate the involvement of nociceptor-related genes and Helicobacter pylori (HP) in the pathogenesis of FD. The expression of nociceptor-related genes was measured in gastric cell lines that were co-cultured with HP. FD patients (n = 117) and controls (n = 55) were enrolled from a tertiary hospital gastroenterology clinic. Expression of the genes nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), and transient receptor potential cation channel subfamily V member 1 (TRPV1) in the gastric mucosa were detected by reverse transcription polymerase chain reaction (RT-PCR), and immunohistochemical staining of TRPV1 was analyzed. These measurements were repeated after 1 year. TRPV1, GDNF, and NGF expression was elevated in gastric cell lines co-cultured with HP. TRPV1 immunostaining was stronger in HP-positive than HP-negative subjects. The FD group showed higher expression levels of TRPV1, GDNF, and NGF and increased TRPV1 immunostaining compared with those of the control group (all P < 0.05). Among 61 subjects who were followed up at 1 year, controls with successful HP eradication and patients whose symptoms had improved both showed significant reductions in the expression of TRPV1 and NGF (all P < 0.05) compared with controls without HP eradication and patients whose symptoms had not improved, respectively. The expression of NGF, GDNF, and TRPV1 may be associated with the pathogenesis of FD. Since HP infection may induce the increased expression of these genes, anti-HP therapy could be beneficial for HP-positive patients with FD.

Gastric cancer development after the successful eradication of Helicobacter pylori.

Gastric cancer (GC) develops as a result of inflammation-associated carcinogenesis due to Helicobacter pylori (H. pylori) infection and subsequent defects in genetic/epigenetic events. Although the indication for eradication therapy has become widespread, clinical studies have revealed its limited effects in decreasing the incidence of GC. Moreover, research on biopsy specimens obtained by conventional endoscopy has demonstrated the feasibility of the restoration of some genetic/epigenetic alterations in the gastric mucosa. Practically, the number of sporadic cases of primary/metachronous GC that emerge after successful eradication has increased, while on-going guidelines recommend eradication therapy for patients with chronic gastritis and those with background mucosa after endoscopic resection for GC. Accordingly, regular surveillance of numerous individuals who have received eradication therapy is recommended despite the lack of biomarkers. Recently, the focus has been on functional reversibility after successful eradication as another cue to elucidate the mechanisms of restoration as well as those of carcinogenesis in the gastric mucosa after H. pylori eradication. We demonstrated that Congo-red chromoendoscopy enabled the identification of the multi-focal distribution of functionally irreversible mucosa compared with that of restored mucosa after successful eradication in individuals at extremely high risk for GC. Further research that uses functional imaging may provide new insights into the mechanisms of regeneration and carcinogenesis in the gastric mucosa post-eradication and may allow for the development of useful biomarkers.

Eradication of Helicobacter pylori Infection Restores ki67, p53, and Cyclin D1 Immunoreactivity in the Human Gastric Epithelium.

INTRODUCTIONWe evaluated the effect of Helicobacter pylori (HP) eradication on p53, cyclin D1 expression, and cell proliferation in gastric mucosa.MATERIALS AND METHODSWe assessed p53, cyclin D1, and ki67 immunoexpression in gastric mucosa from 31 HP chronic gastritis patients and 12 controls. Reassessment was performed 6 months after successful HP eradication.RESULTSSuccessful eradication resulted in significant decrease of p53 (1.53 ± 0.16 vs 0.83 ± 0.19, P = 0.01) and ki67 (9.84 ± 0.96 vs 4.77 ± 0.27, P < 0.001) staining in the antrum. Similarly, p53 immunoreactivity significantly decreased in the corpus (1.27 ± 0.20 vs 0.46 ± 0.15, P = 0.02), while there was a trend for decreased corpus cyclin D1 and ki67 expression (0.17 ± 0.07 vs 0.0, P = 0.08 and 8.71 ± 1.24 vs 5.85 ± 0.54, P = 0.09, respectively). Importantly, after successful HP eradication, the immunoreactivity of the studied parameters was similar to that of controls.CONCLUSIONSuccessful HP infection eradication restores p53, cyclin D1, and ki67 immunoreactivity in the gastric mucosa to the level of controls.

Endoscopic features associated with development of metachronous gastric cancer in patients who underwent endoscopic resection followed by Helicobacter pylori eradication

The preventive effect of Helicobacter pylori (HP) eradication on metachronous gastric cancer development after endoscopic resection remains controversial. The aim of this study was to identify specific endoscopic features that correlated with the risk of metachronous gastric cancer development after endoscopic submucosal dissection (ESD) using both endoscopic findings before ESD and changes of findings after HP eradication. This retrospective study investigated 122 consecutive patients who underwent ESD for early gastric cancer and successful HP eradication after ESD. Endoscopic findings linked with HP before ESD and changes after HP eradication were evaluated according to the development of metachronous cancer. Most patients showed severe atrophy and intestinal metaplasia (IM) before ESD (97% and 83%, respectively). Improvement of spotty redness, improvement of diffuse redness, emergence of patchy redness, and emergence of map-like redness were frequent findings after HP eradication (52%, 50%, 54%, and 32%, respectively). Kaplan-Meier curves indicated that patients without IM before ESD never developed metachronous cancer, while patients with emergence of map-like redness after HP eradication were significantly more likely to develop metachronous cancer (log-rank test, p = 0.031 and p < 0.001, respectively). Multivariate analysis indicated that emergence of map-like redness after HP eradication was the only predictive factor for development of metachronous cancer (hazard ratio, 3.61; 95% confidence interval, 1.41-9.21; p = 0.007). Absence of IM before ESD and emergence of map-like redness after HP eradication were useful endoscopic findings in the negative and positive prediction of metachronous gastric cancer developing after ESD.

Trends in Helicobacter pylori eradication rates by first-line triple therapy and related factors in eradication therapy.

Background/Aims:Trends in successful eradication of Helicobacter pylori using first-line triple therapy, consisting of a proton pump inhibitor, amoxicillin, and clarithromycin, have been understudied. We evaluated H. pylori eradication rates at a single center over the last 10 years and identified risk factors related to eradication failure.Methods:This study included 1,413 patients who were diagnosed with H. pylori infection and received 7 days of triple therapy between January 2003 and December 2012. We investigated H. pylori eradication rates retrospectively with respect to the year of therapy, as well as demographic and clinical factors. H. pylori eradication was confirmed by a 13C-urea breath test or a rapid urease test at least 4 weeks after the completion of triple therapy.ResultsThe overall H. pylori eradication rate was 84.9%. Annual eradication rates from 2003 to 2012 were 93.5%, 80.0%, 87.2%, 88.5%, 92.0%, 88.3%, 85.7%, 84.1%, 83.7%, and 78.8%, respectively, by per-protocol analysis. The eradication rate with first-line triple therapy decreased during the last 10 years (p = 0.015). Multivariate analysis showed that female gender (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.12 to 2.55) and smoking (OR, 1.61; 95% CI, 1.05 to 2.47) were associated with the failure of H. pylori eradication therapy.Conclusions:The efficacy of first-line triple therapy for H. pylori infection has decreased over the last 10 years, suggesting an increase in antibiotic-resistant H. pylori strains. Thus, other first-line therapies may be necessary for H. pylori eradication in the near future.

Activation of Helicobacter pylori causes either autoimmune thyroid diseases or carcinogenesis in the digestive tract.

Helicobacter pylori has been implicated in stimulation of immune system, development of autoimmune endocrinopathies as autoimmune thyroiditis (AT) and on other hand induction of immunosupresion activates gastric and extra-gastric diseases such as gastric ulcer or cancer. It causes persistent lifelong infection despite local and systemic immune response. Our results indicate that Helicobacter pylori might cause inhibition of the specific cellular immune response in Helicobacter pylori-infected patients with or without autoimmune diseases such as AT. We cannot also declare the carcinogenic effect in oropharynx. However the association of any infection agents and cancerogenesis exists. The adherence of Helicobacter pylori expression and enlargement of benign lymphatic tissue and the high incidence of the DNA of Helicobacter pylori in laryngopharyngeal and oropharyngeal cancer is reality. LTT appears to be a good tool for detection of immune memory cellular response in patients with Helicobacter pylori infection and AT. All these complications of Helicobacter pylori infection can be abrogated by successful eradication of Helicobacter pylori.

Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan.

A previous multicenter prospective randomized study from Japan showed that Helicobacter pylori eradication reduced the development of metachronous gastric cancer (MGC) after endoscopic resection for early gastric cancer. MGC risk, however, is not eliminated; yet few studies have evaluated its long-term incidence and risk factors. In this study, we investigated the incidence of and risk factors for MGC in patients who underwent endoscopic resection for early gastric cancer with successful H. pylori eradication. A total of 594 patients who underwent endoscopic resection for early gastric cancer and successful H. pylori eradication at three institutions (National Cancer Center Hospital, University of Tokyo Hospital, and Wakayama Medical University Hospital) were analyzed retrospectively. Annual endoscopic surveillance was performed after initial endoscopic resection. MGC was defined as a gastric cancer newly detected at least 1year after successful H. pylori eradication. Ninety-four MGCs were detected in 79 patients during the 4.5-year median follow-up period. Kaplan-Meier analysis showed the cumulative incidence of MGC 5years after successful H. pylori eradication was 15.0%; the incidence of MGC calculated by use of the person-year method was 29.9 cases per 1000 person-years. Multivariate analysis using the Cox proportional hazards model revealed that male sex, severe gastric mucosal atrophy, and multiple gastric cancers before successful H. pylori eradication were independent risk factors for MGC. Eleven percent of MGCs (10 of 94) were detected more than 5years after successful H. pylori eradication. Surveillance endoscopy for MGC in patients who have undergone endoscopic resection for early gastric cancer should be performed even after successful H. pylori eradication.

Colloidal bismuth subcitrate impedes proton entry into Helicobacter pylori and increases the efficacy of growth-dependent antibiotics.

Successful eradication of Helicobacter pylori is becoming more difficult, mainly due to emerging antibiotic resistance. Treatment regimens containing bismuth have increased efficacy, but the mechanism is unknown. Helicobacter pylori is a neutralophile adapted to survive the acidic gastric environment via acid acclimation, but demonstrates more robust growth at neutral pH. Many antibiotics used to treat H. pylori rely on bacterial growth. To investigate the mechanism of increased efficacy of bismuth-containing H. pylori treatment regimens. RNAseq and qPCR, urease activity in permeabilised and intact bacteria, internal pH and membrane potential were measured with and without colloidal bismuth subcitrate (CBS). Bacterial survival was assessed with CBS and/or ampicillin. Genes involved with metabolism and growth were upregulated in the presence of CBS at acidic pH. Urease activity of permeabilised H. pylori at pH 7.4 and 4.5 decreased in the presence of CBS, but intact urease activity decreased only at acidic pH. The fall in cytoplasmic pH with external acidification was diminished by CBS. The increase in membrane potential in response to urea addition at acidic medium pH was unaffected by CBS. The impact of CBS and ampicillin on H. pylori survival was greater than either agent alone. Bismuth is not acting directly on urease or the urea channel. Colloidal bismuth subcitrate impedes proton entry into the bacteria, leading to a decrease in the expected fall in cytoplasmic pH. With cytoplasmic pH remaining within range for increased metabolic activity of a neutralophile, the efficacy of growth-dependent antibiotics is augmented.

Antibiotic Resistance of

The primary predictor of successful Helicobacter pylori eradication is antibiotic resistance. To assess antibiotic resistance of H. pylori strains

275 Outcome Over 5 Years of Minimally Invasive Treatment of Early Gastric Cancer Beyond Endoscopic Submucosal Dissection

275 Outcome Over 5 Years of Minimally Invasive Treatment of Early Gastric Cancer Beyond Endoscopic Submucosal Dissection

276 Incidence and Risk Factors of Metachronous Gastric Cancer After Endoscopic Resection and Successful Helicobacter pylori Eradication: Results From a Large-Scale, Multicenter Cohort Study in Japan

A previous multicenter prospective randomized study from Japan showed that Helicobacter pylori (HP) eradication reduced the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) for early gastric cancer (GC) from 40.5 to 14.1 cases per 1000 person-years. MGC is, however, still detected in a certain rate even after successful HP eradication, few studies have evaluated the incidence and risk factors of MGC.

Su1181 Combination Therapy With Eradication Agents Is Useful for Successful Eradication of Helicobacter pylori in Japan

Background: Eradication therapy for Helicobacter pylori-related chronic gastritis was approved for coverage by the Japanese national insurance in February 2013. Therefore, the use of eradication therapy has rapidly increased in Japan. The primary eradication rate of H. pylori using the 7-day triple therapy has gradually decreased in recent years. Drug resistance to clarithromycin (CAM), poor treatment compliance, and smoking are factors associated with eradication failure. A recent study showed that combination of eradication agents is useful for increasing eradication success, because combination treatments are prepared using daily dosages on one sheet. In our study, we prospectively compared the eradication rate in patients receiving conventional therapy with three drugs to that in patients receiving combination therapy. Patients and methods: Between July 2012 and September 2013, we included 276 patients (147 men and 129 women; mean age, 62.2 years) with H. pylori-positive peptic ulcers and gastritis. Combination therapy (Lansap®; lansoprazole 30 mg plus amoxicillin 750 mg plus CAM 200 mg) was administered to 54 patients twice a day for 7 days, and conventional therapy (omeprazole 20 mg or esomeprazole 20 mg or rabeprazole 20 mg plus amoxicillin 750 mg plus CAM 200 mg) was administered to 221 patients as individual drugs twice a day for 7 days. The 13C-urea breath test was used to confirm the eradication of H. pylori at least 6 weeks after the completion of eradication therapy. Patients who had undergone H. pylori eradication therapy in the past and patients who used proton pump inhibitors and antibiotics within 4 weeks were excluded. Results: No significant difference was observed in the background criteria of patients between the combination group and conventional group. The eradication rate (per protocol analysis) in the combination group was 90.3% (47/52), which was significantly different from that in the conventional group (74.9%; 161/215; p< 0.01). In addition, the eradication rate in intention-to-treat (ITT) analysis was significantly higher in the combination group (85.4%, 47/55) than in the conventional group (72.8%, 161/221; p< 0.01). No significant difference was observed in the incidence of adverse drug reactions (such as diarrhea, dysgeusia, and eruption) between the two groups (combination group 4.1%; conventional group 4.7%). Conclusions: Our study suggested that combination therapy with eradication agents is more useful for successful eradication of H. pylori than conventional therapy, although the primary eradication rate has decreased in Japan in the recent years. The underlying reason for the decrease in the primary eradication rate might be greater compliance to combination therapy.

Sa1666 The Incidence and Risk Factors of Metachronous Gastric Cancer After Endoscopic Resection and Successful Helicobacter pylori Eradication; Results From a Large-Scale Population-Based Cohort Study in Japan

Sa1666 The Incidence and Risk Factors of Metachronous Gastric Cancer After Endoscopic Resection and Successful Helicobacter pylori Eradication; Results From a Large-Scale Population-Based Cohort Study in Japan

Sa1602 Magnifying Narrow-Band Imaging of Surface Maturation in Early Differentiated-Type Gastric Cancers After Helicobacter pylori Eradication

Even after successful Helicobacter pylori eradication, primary or metachronous gastric cancers are sometimes discovered. As the use of eradication therapy becomes more widespread, these gastric cancers increase in clinical practice. After successful eradication, inflammatory activity is controlled in both the surrounding non-cancerous mucosa and cancerous mucosa. Conventional white-light endoscopy thus may not accurately differentiate and diagnose these gastric cancers. Characteristic findings for such lesions in terms of narrow-band imaging with magnifying endoscopy (NBI-ME) and histopathology need to be clarified to allow accurate diagnosis.

Prevalence of Helicobacter pylori and its recurrence after successful eradication in a developing nation (Morocco)

In developed countries, reinfection after successful eradication of Helicobacter pylori appears unusual. High prevalences of H. pylori in developing countries may result in high reinfection rates. In Morocco, published studies regarding the prevalence of H. pylori are limited, and to our knowledge, there are no data regarding the reinfection rate of H. pylori after successful treatment. The aim of this study was to determine the prevalence of H. pylori in our area, and the reinfection rate at 6 months and 1 year of follow-up after successful eradication. Consecutive patients with investigated ulcer or non-ulcer dyspepsia were prospectively enrolled in the Hassan II University Hospital of Fez. Patients with H. pylori infection were treated with a 1-week triple therapy or 10 day sequential therapy. Those tested urea breath test negative after 3 months of treatment were followed prospectively with repeated urea breath test at 6 months and 1 year. H. pylori status at endoscopic examination was determined by rapid urease test, histology, and culture. Four hundred and twenty-nine patients were enrolled in the study, among them 324 patients (75.5%) presented with H. pylori infection. Two hundred and fifty-six (83.3%) patients had successfully eradicated H. pylori following treatment, among them, two patients (0.8%) were reinfected with H. pylori over 12 months. The rate of reinfection was 0.42% in the first 6 months and of 0.45% in the first year of the study. The results of the present study demonstrate that firstly, prevalence of H. pylori is high (75.5%) in our area, secondly as in developed countries, there is a low (0.8%) but continuous risk of H. pylori infection in adulthood. A different approach for follow-up after H. pylori eradication is probably needed in patients of developing countries, since reinfection prevalence is different between countries.

Magnifying narrow-band imaging of surface maturation in early differentiated-type gastric cancers after Helicobacter pylori eradication

Even after successful Helicobacter pylori eradication, primary or metachronous gastric cancers are sometimes discovered. The endoscopic features of these cancers may be modified by controlling inflammation. Characteristic findings for such lesions in terms of narrow-band imaging with magnifying endoscopy (NBI-ME) and histopathology need to be clarified to allow accurate diagnosis. Distinctive NBI-ME characteristics were examined retrospectively in intramucosal or minimally submucosal and differentiated-type adenocarcinomas from a successful eradication group (42 patients, 50 lesions) and a non-eradicated control group (44 patients, 50 lesions) matched in age and sex. A "gastritis-like" appearance under NBI-ME was characterized by uniform papillae and/or tubular pits with a whitish border, regular or faint microvessels and unclear demarcation, resembling the adjacent noncancerous mucosa. Histological differentiation at the luminal surface of the cancer was evaluated according to Ki-67 immunoreactivity restricted at the middle or lower portion of the tubules. NBI-ME alteration was prospectively confirmed in 29 patients (30 lesions) after eradication therapy. The frequency of a "gastritis-like" appearance was 44% (22/50) for the eradication group, which was significantly higher than the 4% (2/50) for the control group (p < 0.001). In the eradication group, the "gastritis-like" appearance was significantly correlated with histological surface differentiation (p < 0.001). In the prospective study, NBI-ME showed changes to heterogeneous papillary microstructures in 43% (10/23) of the lesions after successful eradication at short-term follow-up. Identification of surface maturation under NBI-ME offers a promising approach for accurate diagnosis of early gastric cancers after successful eradication.