Metaplastic Gastritis Research Articles

Clinicopathologic Features of Autoimmune Metaplastic Atrophic Gastritis (AMAG) in an Underserved Community

Abstract Introduction/Objective Autoimmune metaplastic gastritis (AMAG), typically associated with pernicious anemia and subsequent risk of gastric neoplasia, is an entity often underrecognized in routine gastric biopsies and can lead to delay in the diagnosis and management of patients. In this study, we analyze the demographics and clinical features of AMAG in an inner city, underserved population with histopathologic and serologic correlation. Methods/Case Report We retrospectively collected data on patients diagnosed with or with probable AMAG over a 29-month period from Jan 2020-May 2022 and correlated the histopathology with demographics and clinical presentation. We retrieved prior biopsies on available cases. Results (if a Case Study enter NA) Our Data Demonstrates: -Almost equal prevalence of AMAG in African American and Caucasian patients, with a higher rate of incidence in older population (68% over the age of 60 years), and in female patients. -43.5% had antibody testing and only 25% of patients had testing for Gastrin levels, but the diagnosis of AMAG was frequently associated with a positive laboratory finding (78.7% and 74.3%, respectively) when performed. -57.8% had clinically documented anemia, among those, 88.9% had microcytic or normocytic anemia. Only 11.1% had macrocytic anemia -A history of prior biopsies demonstrating chronic gastritis was seen in 33% of patients. Conclusion Our study demonstrates that patients with AMAG come from diverse backgrounds and frequently lack laboratory findings typically associated with pernicious anemia at the time of diagnosis. As such, pathologists and gastroenterologists may benefit from a lower threshold when considering which patients to evaluate for AMAG. Complete laboratory evaluations were infrequent, which is a limitation, but this may be secondary to a lack of clinical knowledge regarding appropriate testing and an underserved patient population which lacks good continuity of care.

Upper Gastrointestinal Tract Associated Lesions in Patients with Newly Diagnosed Celiac Disease

(1) Background: Currently available guidelines require upper gastrointestinal (GI) endoscopy with biopsy sampling for adult celiac disease (CD) diagnosis. Based on the pediatric experience, there has been a growing interest if serology-based diagnosis would be possible for adult CD also. Our aim was to analyze the associated upper GI tract lesions in newly diagnosed CD patients, to see if significant associated pathology is detected during index endoscopy, which might impact patient management not related to CD. (2) Methods: We performed a retrospective analysis of newly diagnosed CD cases diagnosed over a period of 7 years (2014–2020). Demographic, clinical, laboratory, endoscopy and histopathology data were collected from the patients’ charts. Diagnosis was set according to ACG Guideline 2013. (3) Results: Altogether 79 patients were recruited for this study purpose, 75.9% female, median age 39 years. All patients had positive CD-specific serology and atrophic mucosal injury in duodenal biopsy samples. Besides villous atrophy, associated endoscopic findings were detected in 42/79 (53.16%) of patients. Most of the gastric lesions were minor endoscopic findings—small sliding hiatal hernias, non-specific chronic gastritis, but we also found two cases of peptic ulcers, one case of metaplastic gastritis, six cases of atrophic gastritis and one subepithelial lesion. Only one patient had changes in the duodenum except CD-related findings—an inflammatory polyp in the duodenal bulb. No malignancies were found. (4) Conclusions: In our cohort, there was a significant number of newly diagnosed CD patients who had associated lesions during the index upper GI endoscopy, but most of them were minor endoscopic findings.

Helicobacter pylori-negative Gastric Cancer

<i>Helicobacter pylori (H. pylori)</i>-negative gastric cancer is diagnosed when gastric malignancies are found in patients in <i>H. pylori</i>-naïve stomachs. There are four types of noncardiac <i>H. pylori</i>-negative gastric cancers. The signet ring cell-type poorly cohesive carcinoma is most common, followed by the chief cell-predominant type gastric adenocarcinoma of the fundic gland. Extremely well-differentiated adenocarcinoma of the corpus and well-differentiated pyloric gland cancers are rare outside Japan because of country-specific differences in diagnostic criteria. In endemic areas of <i>H. pylori</i> infection, strict criteria are required for diagnosing an <i>H. pylori</i>-naïve stomach. Both invasive and noninvasive <i>H. pylori</i> tests should show negative results in a subject without a history of <i>H. pylori</i> infection. Furthermore, the serum pepsinogen (PG) assay and endoscopic findings of the background gastric mucosa are required to discriminate subjects with past infections owing to spontaneous regression or unintended eradication of <i>H. pylori</i>. There should be no gastric corpus atrophy (PG I ≤70 ng/mL and PG I/II ≤3.0). Gastroscopy should reveal a regular arrangement of collecting venules without gastric xanthoma, metaplastic gastritis, or advanced atrophy over the angle. On biopsy, there should be no gastric atrophy, intestinal metaplasia, neutrophils, or <i>H. pylori</i> infiltration, and only a mild degree of mononuclear cell infiltration is permitted. The types and characteristics of noncardiac <i>H. pylori</i>-negative gastric cancers are summarized in this review, along with current diagnostic challenges found in Korea.

The role of linked color imaging in endoscopic diagnosis of Helicobacter pylori associated gastritis

Objective Linked color imaging (LCI), a novel image-enhanced endoscopy, can make it easy to recognize differences in mucosal color. It may be helpful for diagnosing H. pylori associated gastritis and H. pylori infection status. We investigated whether LCI could improve the diagnostic accuracy of H. pylori associated gastritis. Materials and methods Upper endoscopy was performed for 100 patients using white light imaging (WLI) and LCI. During the exam, endoscopic video was recorded. It was then analyzed by four expert endoscopists. They reviewed these videos for endoscopic diagnosis of atrophic gastritis, metaplastic gastritis, nodular gastritis and H. pylori infection. Tissue biopsies with rapid urease test were done to confirm H. pylori infection status and intestinal metaplasia. Results Kappa values for the inter-observer variability among the four endoscopists were fair to moderate under WLI and fair to good under LCI. Sensitivity, specificity, positive predictive value and negative predictive value for diagnosing H. pylori infection using WLI were 32.4%, 93.3%, 85.2% and 53.6%, respectively, while those for LCI were 57.4%, 91.3%, 88.7% and 64.3%, respectively. Total diagnostic accuracies for diagnosing H. pylori infection using WLI/LCI were 70.8%/78.8%. The accuracy and sensitivity of LCI for diagnosing H. pylori infection were significantly higher than those of WLI (p < .001 for both). However, there were no significant differences in the accuracy, sensitivity or specificity for diagnosing metaplastic gastritis between LCI and WLI. Conclusions LCI has better diagnostic accuracy for H. pylori infection status than WLI. Clinical trial registration number: KCT0003674.

ABC Classification Is Less Useful for Older Koreans Born before 1960.

Background/AimsIn the ABC classification system, group A consists of seronegative subjects without gastric corpus atrophy. This study aimed to determine the prevalence and characteristics of pseudo group A subjects.MethodsGroup A subjects were identified among consecutive Korean adults who underwent a serum anti-Helicobacter pylori immunoglobulin G (IgG) test and pepsinogen (PG) assay on the day of endoscopy. Past infection was defined as the presence of either eradication history or endoscopic findings suggesting past infection (i.e., gastric xanthoma, metaplastic gastritis, or advanced atrophy >closed-type 1).ResultsAmong 2,620 group A subjects, 448 (17.1%) had eradication history, and 133 (5.1%) showed endoscopic findings suggesting past infection. Older age (odds ratio [OR], 1.148; 95% confidence interval [CI], 1.067 to 1.236) and earlier year of birth (OR, 1.086; 95% CI, 1.009 to 1.168) were independent risk factors for classification into pseudo group A, with cutoff points at 50.5 years and birth year of 1959.5, respectively. Positive H. pylori test findings were found in 22 subjects (3.1%) among the 715 subjects who underwent the urea breath test or Giemsa staining on the same day. Current infection was positively correlated with PG I and PG II levels (p<0.001) but not with age, anti-H. pylori IgG titer, or classification into pseudo group A.ConclusionsAmong the group A subjects, 22.2% had past infection. The risk was higher in subjects older than 50 years, especially those born before 1960. Furthermore, current infection was found in 3.1% of the subjects and was correlated with increased gastric secretory ability.

Nodular Gastritis as a Precursor Lesion of Atrophic and Metaplastic Gastritis

Chronic atrophic gastritis (CAG) and metaplastic gastritis (MG) are precancerous conditions of Helicobacter pylori (H. pylori)-related gastric cancer. This study aimed to identify the characteristics of nodular gastritis (NG) showing CAG or MG after nodule regression. H. pylori-infected patients with NG were included after upper gastrointestinal endoscopy. Patients were excluded if their latest endoscopy had been performed ≤36 months after the initial diagnosis of NG. Small-granular-type NG was defined as the condition with 1-2 mm regular subepithelial nodules. Large-nodular-type NG was defined as those with 3-4 mm, irregular subepithelial nodules. The endoscopic findings after nodule regression were recorded. Among the 97 H. pylori-infected patients with NG, 61 showed nodule regression after a mean follow-up of 73.0±22.0 months. After nodule regression, 16 patients showed a salt-and-pepper appearance and/or transparent submucosal vessels, indicating CAG. Twenty-nine patients showed diffuse irregular elevations and/or whitish plaques, indicating MG. Sixteen patients with other endoscopic findings (14 normal, one erosive gastritis, and one chronic superficial gastritis) showed a higher proportion of H. pylori eradication (12/16, 75.0%) than those in the CAG group (5/16, 31.3%) and MG group (6/29, 20.7%; p=0.001). Patients with small-granular-type NG tended to progress toward CAG (14/27, 51.9%), whereas those with large-nodular-type NG tended to progress toward MG (25/34, 73.5%; p<0.001). In patients with a persistent H. pylori infection, NG tended to progress to CAG or MG when the nodules regressed. Small-granular-type NG tended to progress to CAG, whereas large-nodular-type NG tended to progress to MG.

Gastric cancer & prospectsof cancer in Saudi Arabia peninsula.

Gastric cancer is classified to be an aggressive disease with poor treatment outcome, as most cases remain undetected until later stages, wherein surgery and few chemotherapeutics become the only recommended treatment course. The process of cancer development is multistep involving many stages and types of precancerous lesions, and hence, routine monitoring becomes a necessity in those detected with these or exposed to risk factors. Studying the pattern of gastric cancer for any geographical region is also important to control mortality and focus on implementation of efficient management and treatment guidelines. The cause for gastric cancer can be genetic, racial as well as environmental, and hence the pattern of this malignancy differs across geographical regions and between the developing and the developed nations. In case of the Kindgom of Saudi Arabia, very few hospital-based reports have been published highlighting the pattern of gastric cancer, and the associated incidence and mortality rates. However, classified to be one of the most crucial cancer forms in Saudi Arabia, research pertaining to epidemiology, presentation and pathological features are limited. Studying gastric cancer occurrence from public health viewpoint is important also because eradication of causative agents like those that H. pylori has also shown been not reduce the risk of cancer development among individuals with atrophic metaplastic gastritis. In case of Saudi Arabia, many inherent risks for this malignancy exists like waterpipe smoking and shift in diet pattern from the traditional Mediterranean diet. Our review focusses on pattern of gastric cancer on a global scale in comparison to scenario in Saudi Arabia. The aim is to encompass all of the less stressed upon facts about this malignancy in the Kingdom, paving way for future work in this regards.

Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond.

Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents.

Link between Serum Pepsinogen Concentrations and Upper Gastrointestinal Endoscopic Findings.

The serum pepsinogen (PG) assay findings are correlated with the status of Helicobacter pylori infection, but there are controversies on the link with upper gastrointestinal (UGI) endoscopic findings. The aim of this study was to determine the significance of a serum PG assay for correlating with endoscopic findings in H. pylori-seroprevalent adult population. Korean adults who visited for a health check-up were included consecutively. Subjects after gastrectomy or H. pylori eradication were excluded. After completing the serum PG assay and anti-H. pylori immunoglobulin G (IgG) titer on the same day of UGI endoscopy, subjects with equivocal serology test finding or gastric neoplasm were excluded. Of the 4,830 included subjects, 3,116 (64.5%) were seropositive for H. pylori. Seropositive finding was related to high serum PG I (P < 0.001) and PG II (P < 0.001) concentrations, low PG I/II ratio (P < 0.001), old age (P < 0.001), and male gender (P = 0.006). After adjusting age and gender, the serum PG I and II concentrations were positively correlated with the presence of nodular gastritis (NG) (all P = 0.003). The serum PG I was positively correlated with gastric ulcer (P = 0.003), and it was correlated with duodenal ulcer in seropositive subjects (P = 0.008). The PG I/II ratio was positively correlated with erosive esophagitis, while it was inversely related to chronic atrophic gastritis and metaplastic gastritis (all P < 0.001). Our findings suggest that the serum PG assay finding correlates well with the UGI endoscopic finding. A higher serum PG concentration in subjects with NG and peptic ulcer disease suggests that endoscopic findings reflect gastric secreting ability.

Endoscopic gastritis, serum pepsinogen assay, and Helicobacter pylori infection.

Endoscopic findings of the background gastric mucosa are important in the Helicobacter pylori-seroprevalent population. It is strongly correlated not only with the risk of gastric cancer, but also with the excretion ability of gastric mucosa cells. In noninfected subjects, common endoscopic findings are regular arrangement of collecting venules, chronic superficial gastritis, and erosive gastritis. In cases of active H. pylori infection, nodularity on the antrum, hemorrhagic spots on the fundus, and thickened gastric folds are common endoscopic findings. The secreting ability of the gastric mucosa cells is usually intact in both noninfected and actively infected stomachs, and the intragastric condition becomes hyperacidic upon inflammation. Increased serum pepsinogen II concentration correlates well with active H. pylori infection, and also indicates an increased risk of diffuse-type gastric cancer. In chronic inactive H. pylori infection, metaplastic gastritis and atrophic gastritis extending from the antrum (closed-type chronic atrophic gastritis) toward the corpus (open-type chronic atrophic gastritis) are common endoscopic findings. The intragastric environment is hypoacidic and the risk of intestinal-type gastric cancer is increased in such conditions. Furthermore, there is a decrease in serum pepsinogen I concentration when the secreting ability of the gastric mucosa cells is damaged. Serologic and endoscopic changes that occur upon H. pylori infection are important findings for estimating the secreting ability of the gastric mucosa cells, and could be applied for the secondary prevention of gastric cancer.

Prevalence of Precancerous Conditions and Gastric Cancer Based upon the National Cancer Screening Program in Korea for 7 Years, Single Center Experience.

Aims. Gastric cancer is the second most prevalent cancer and the third leading cause of cancer-related deaths in Korea. The National Cancer Screening Program (NCSP) has implemented esophagogastroduodenoscopy (EGD) biennially for all Koreans starting in their 40s. This study was conducted to estimate the clinical relevance of NCSP through identifying the prevalence of gastric disease, including cancer. Materials and Methods. Data from 40,821 subjects who received the screening EGD in the single center for 7 years were retrospectively investigated. Results. The overall prevalence of nonatrophic/atrophic/metaplastic gastritis, peptic ulcer, adenoma, early gastric cancer (EGC), and advanced gastric cancer (AGC) was 44.28%, 27.97%, 14.95%, 0.59%, 0.43%, 0.21%, and 0.09%, respectively. The prevalence of metaplastic gastritis, peptic ulcer, adenoma, EGC, and AGC was significantly higher in men than in women. The prevalence of preneoplastic/neoplastic disease significantly increased with age. Judged from the ratio of EGC to AGC, the proportion of EGC made up to 70% of all cancers. Conclusions. Screening endoscopy starting for people in their 40s should be strongly recommended for the elderly. Through the NCSP, the early detection of gastric cancer might contribute to the decreased mortality rate due to gastric cancer in Korea.

Su1155 Benefit of Helicobacter pylori Eradication Therapy to Symptomatology Is Greater in Patients Without Metaplastic Gastritis

Background: Improvements to dyspeptic symptoms after medication is often incomplete, and thus controversy exists over the use of Helicobacter pylori eradication therapy in nonulcer dyspepsia. This study analyzed the factors predictive of the benefits to symptomatology after H. pylori eradication. Methods: Consecutive patients presenting with dyspeptic symptoms were included in a prospective setting. Metaplastic gastritis was diagnosed by endoscopic findings with a gastric biopsy. The urea breath test (UBT) was performed 4 weeks after H. pylori eradication by a 7-day course of pantoprazole, amoxicillin and clarithromycin. A positive UBT resulted in a subsequent 7-day course of pantoprazole, bismuth, tetracycline, and metronidazole. The patients were asked to score five major symptoms (epigastric pain, early satiety, postprandial fullness, bloating, and nausea) as 0 (none), 1 (rare), 2 (intermittent), 3 (frequent) to 4 (always) before and after the successful eradication. Results: Of 153 H. pylori-infected subjects, 120 patients were successfully eradicated after first-line therapy, with second-line therapy being successful in the remaining 31 patients and third-line therapy using fluoroquinolone in 2 patients. The symptoms persisted after the eradication in 28 (54.9%) of 51 metaplastic gastritis patients and in 24 (23.5%) of 102 non-metaplastic gastritis patients (p<0.001). Early satiation (p<0001), postprandial fullness (p=0.004), and bloating (p=0.002) showed less improvement in metaplastic gastritis patients than in nonmetaplastic gastritis patients after H. pylori eradication. Conclusions: The benefit to symptomatology is more pronounced in dyspeptic patients without metaplastic gastritis than in those with metaplastic gastritis. This represents further evidence that H. pylori eradication should be considered in patients before metaplastic gastritis develops.

Su1158 Comparative Study of Helicobacter pylori Eradication Rates With 10-Day Quadruple “Concomitant” Therapy and 10-Day “Sequential” Therapy

Background: Improvements to dyspeptic symptoms after medication is often incomplete, and thus controversy exists over the use of Helicobacter pylori eradication therapy in nonulcer dyspepsia. This study analyzed the factors predictive of the benefits to symptomatology after H. pylori eradication. Methods: Consecutive patients presenting with dyspeptic symptoms were included in a prospective setting. Metaplastic gastritis was diagnosed by endoscopic findings with a gastric biopsy. The urea breath test (UBT) was performed 4 weeks after H. pylori eradication by a 7-day course of pantoprazole, amoxicillin and clarithromycin. A positive UBT resulted in a subsequent 7-day course of pantoprazole, bismuth, tetracycline, and metronidazole. The patients were asked to score five major symptoms (epigastric pain, early satiety, postprandial fullness, bloating, and nausea) as 0 (none), 1 (rare), 2 (intermittent), 3 (frequent) to 4 (always) before and after the successful eradication. Results: Of 153 H. pylori-infected subjects, 120 patients were successfully eradicated after first-line therapy, with second-line therapy being successful in the remaining 31 patients and third-line therapy using fluoroquinolone in 2 patients. The symptoms persisted after the eradication in 28 (54.9%) of 51 metaplastic gastritis patients and in 24 (23.5%) of 102 non-metaplastic gastritis patients (p<0.001). Early satiation (p<0001), postprandial fullness (p=0.004), and bloating (p=0.002) showed less improvement in metaplastic gastritis patients than in nonmetaplastic gastritis patients after H. pylori eradication. Conclusions: The benefit to symptomatology is more pronounced in dyspeptic patients without metaplastic gastritis than in those with metaplastic gastritis. This represents further evidence that H. pylori eradication should be considered in patients before metaplastic gastritis develops.

Sa1630 the Prevalence of Gastric Preneoplastic Lesions in East Asians and Hispanics in the United States Parallels the Incidence of Gastric Cancer in Their Corresponding Ancestral Countries

While the epidemiology of H. pylori infection and the incidence of gastric cancer (GC) and its precursor lesions in different countries are well established, the consequences of such variability for the healthcare of the multi-ethnic population of the U.S. are less clear and have not been systematically investigated. The aim of this study was to compare the prevalence of H. pylori infection and atrophic metaplastic gastritis in U.S. residents of East Asian and Hispanic ancestry to a group of U.S. residents not identified with either group.

Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer

Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects.

Helicobacter pylori infection and gastric carcinogenesis in rodent models

Helicobacter pylori infection is an important factor for gastric carcinogenesis in human. In carcinogen-treated Mongolian gerbils, H. pylori infection enhances stomach carcinogenesis, while infection alone induced severe hyperplasia called heterotopic proliferative glands. A high-salt diet or early acquisition of the bacteria exacerbates inflammation and carcinogenesis. Oxygen radical scavengers or anti-inflammatory chemicals as well as eradication of H. pylori are effective to prevent carcinogenesis. H. pylori-associated inflammation induces intestinal metaplasia and intestinalization of stomach cancers independently. It is necessary to control cancer development not only in H. pylori-positive cases but also in H. pylori-negative metaplastic gastritis.

Endoscopic Gastritis: What Does It Mean?

One can confidently assume that there is no evidence of endoscopic gastritis when the gastric mucosa has a regular pinkish color without discoloration or structural alteration, the gastric rugae are not thicker than 5 mm, and if the gastric mucosa expands well upon inflation with air. However, inflammatory changes induce subsequent apoptosis and gland damage, which can lead to regeneration, fibrosis, or metaplasia [1]. Inflammatory changes such as color and/or structural changes are noted in endoscopic findings, and are thus labeled endoscopic gastritis. Endoscopic gastritis can be classified into seven types: (a) superficial, (b) hemorrhagic, (c) erosive, (d) verrucous, (e) atrophic, (f) metaplastic, and (g) hypertrophic [2]. Erosive gastritis is diagnosed when endoscopy reveals small elevations with central umbilication, mimicking octopus’ suckers, which are usually observed in the antrum. It can also be defined as a flat or minimally depressed white spot surrounded by a reddish area that is sometimes accompanied by small superficial bleeding [3]. Since the distinction between erosion and tiny shallow ulcer is arbitrary, the latter might be included under the term ‘‘erosion.’’ When the erosion is elevated, it is generally defined as verrucous gastritis or gastritis varioliformis rather than as erosive gastritis. In this issue of Digestive Diseases and Sciences, Yamamoto et al. [3] provide an interesting finding that lower serum levels of adiponectin are associated with an increased risk of endoscopic erosive gastritis, independently of body mass index (BMI). BMI is known to be associated with abnormal upper endoscopic findings, such as erosive gastritis, gastric ulcer, duodenal ulcer, and reflux esophagitis [4]. Interestingly, when Yamamoto et al. analyzed factors including age, sex, alcohol habits, smoking habits, BMI, blood pressure, cholesterol, triglyceride, glucose, and insulin in 2,400 participants, BMI was significantly higher and the serum adiponectin level was significantly lower in gastritis-positive participants than in gastritis-negative participants. That study indicated a possible role of hypoadiponectinemia in erosive gastritis, in addition to a previous study that showed a link between low plasma adiponectin levels and gastric cancer [5]. Erosive gastritis has been considered relatively less significant than Helicobacter pylori-related endoscopic gastritis, since H. pylori infection involves a multistep progression from gastritis to glandular atrophy, intestinal metaplasia (IM), dysplasia, and ultimately to intestinaltype gastric cancer [6]. We have recently shown that the endoscopic diagnosis of open-type atrophic gastritis is related to the histological diagnosis of IM and Cdx2 expression [7]. Higher levels of Cdx2 expression are related to open-type atrophic gastritis and metaplastic gastritis, but not to closed-type atrophic gastritis and nonatrophic/ nonmetaplastic cases. The location of the atrophic gastric border was found to be strongly related to histological IM and Cdx2 expression. Our findings suggest that Cdx2 expression is an early change that is correlated with the presence of histological IM, and which occurs before endoscopic metaplastic gastritis, and that the risk of development of intestinal-type gastric cancer will continue to remain high during the process of gastric carcinogenesis in open-type atrophic gastritis and metaplastic gastritis, but not in closed-type atrophic gastritis and nonatrophic/ S.-Y. Lee (&) Department of Internal Medicine, Konkuk University School of Medicine, Seoul 143-729, Korea e-mail: sunyoung@kuh.ac.kr

15-Hydroxyprostaglandin Dehydrogenase is Downregulated and Exhibits Tumor Suppressor Activity in Gastric Cancer

We investigated the tumor suppressor activity and regulatory mechanism of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in gastric cancer; 15-PGDH expression was lost in 70.1% of malignant human gastric tissues, but was preserved in normal and metaplastic gastritis. KATO III and SNU-719 cells were transfected with pcDNA3.1-empty vector or an expression vector encoding wild-type 15-PGDH. In TUNEL assays apoptotic cell numbers were increased in KATO-PGDH-WT cells compared with control. We found that EGFR and ERK1/2 inhibitors clearly increased the expression of 15-PGDH in KATO III cells. Our findings demonstrate both downregulation and a tumor suppressor activity of 15-PGDH in gastric cancer.

Endoscopic Diagnosis of Open-Type Atrophic Gastritis Is Related to the Histological Diagnosis of Intestinal Metaplasia and Cdx2 Expression

Long-term Helicobacter pylori infection results in atrophic gastritis and intestinal metaplasia (IM) with Cdx2 expression. We have tried to determine if there was a link between endoscopic and histological diagnosis of IM based on the status of aberrant Cdx2 expression. One hundred and one subjects agreed to upper gastrointestinal endoscopic examination, with biopsy sampling for histology, Giemsa, and Cdx2 immunohistochemical staining before and after the treatment. On endoscopic examination, atrophic gastritis was defined as discoloration with blood vessel transparency, and was classified as either closed or open. Metaplastic gastritis was defined by the presence of whitish patches, whitish plaques, and/or homogeneous whitish discoloration. Histologic analysis was performed to determine H. pylori density, intensity of acute polymorphonuclear cell infiltrates and chronic mononuclear infiltrates, gastric atrophy, and IM as demonstrated using immunohistochemistry for cdx2. Cdx2 protein expression (P=0.018) and the prevalence of histologically detected IM (P=0.011) were higher in cases of endoscopically diagnosed open-type atrophic gastritis and metaplastic gastritis than in closed-type atrophic gastritis and nonatrophic/nonmetaplastic cases. The degree of activity (P=0.006) and inflammation (P=0.007) improved significantly after four weeks of successful H. pylori eradication treatment, whereas the degree of atrophy, metaplasia, and Cdx2 expression did not. Unlike endoscopic diagnosis of closed-type atrophic gastritis, that of open-type atrophic gastritis is highly correlated with the histological diagnosis of IM and Cdx2 expression. Endoscopically diagnosed open-type atrophic gastritis and endoscopically diagnosed metaplastic gastritis have similar histological features, which suggests that a high percentage of IM cases are diagnosed as open-type atrophic gastritis by endoscopic examination.

Preventive effects of etodolac, a selective cyclooxygenase‐2 inhibitor, on cancer development in extensive metaplastic gastritis, a Helicobacter pylori‐negative precancerous lesion

The present study investigated the preventive effects of etodolac, a selective cyclo-oxygenase (COX)-2 inhibitor, on metachronous cancer development after endoscopic resection of early gastric cancer. Among 267 early gastric cancer patients who underwent endoscopic resection, 47 patients with extensive metaplastic gastritis were selected based on endoscopic findings and our previously described criteria of serum pepsinogen (PG) test-positive and Helicobacter pylori antibody-negative conditions. Nonrandomized etodolac treatment (300 mg/day) was administered to 26 patients (Group A), while the remaining 21 patients were untreated (Group B). No significant differences in age, sex distribution, lifestyle factors or extent of metaplastic gastritis at baseline were identified between groups. Patients were followed for metachronous cancer development with endoscopy every 6-12 months for up to 5 years. Mean (standard deviation) follow-up period was 4.2 (0.9) years. In Group B, 5 cancers developed (incidence rate = 6,266/100,000 person-years), significantly more than the 1 cancer in Group A (incidence rate = 898/100,000 person-years; p < 0.05). Long-term etodolac treatment did not influence the extent of metaplastic gastritis as revealed by endoscopic findings or by serum PG levels, but effectively reduced metachronous cancer development in patients with extensive metaplastic gastritis. These results strongly suggest that chemoprevention of cancer in the metaplastic stomach is possible by controlling COX-2 expression.