Degree Of Intestinal Metaplasia Research Articles

Artificial intelligence for evaluating the risk of gastric cancer: reliable detection and scoring of intestinal metaplasia with deep learning algorithms

Gastric cancer (GC) is associated with chronic gastritis. To evaluate the risk, the Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) system was constructed and showed a higher GC risk in stage III or IV patients, determined by the degree of intestinal metaplasia (IM). While the OLGIM system is useful, evaluating the degree of IM requires substantial experience to produce precise scoring. Whole-slide imaging is becoming routine, but most artificial intelligence (AI) systems in pathology are focused on neoplastic lesions. Hematoxylin and eosin-stained slides were scanned. Images were divided into each gastric biopsy tissue and labelled with an IM score. IM was scored as follows: 0 (no IM), 1 (mild IM), 2 (moderate IM), and 3 (severe IM). Overall, 5,753 images were prepared. A deep convolutional neural network (DCNN) model, ResNet50, was used for classification. ResNet50 classified images with and without IM with a sensitivity of 97.7% and specificity of 94.6%. IM scores 2 and 3, those are involved as criteria of stage III or IV in the OLGIM system were classified by ResNet50 in 18 %. The respective sensitivity and specificity values of classifying IM between scores 0, 1, and 2, 3 were 98.5% and 94.9%. The IM scores classified by pathologists and the AI system were different in only 438 (7.6%) of all images, and we found that ResNet50 tended to miss small foci of IM, while it successfully identified minimal IM areas that pathologists missed during the review. Our findings suggested that this AI system would contribute to evaluating the risk of gastric cancer accuracy, reliability, and repeatability with worldwide standardization.

Endoscopic scoring system for gastric atrophy and intestinal metaplasia: correlation with OLGA and OLGIM staging: a single-center prospective pilot study in Korea

Background/Aims We aimed to develop an endoscopic scoring system to evaluate gastric atrophy and intestinal metaplasia using narrow-band imaging (NBI) and near focus mode (NFM) to compare endoscopic scores with the Operative link for gastritis assessment (OLGA) and the Operative link for gastric intestinal metaplasia assessment (OLGIM). Methods A total of 51 patients who underwent diagnostic esophagogastroduodenoscopy were prospectively enrolled and endoscopic scoring using NBI and NFM was performed. Four areas (the lesser and greater curvatures of the antrum and the lesser and greater curvature side of the corpus) were observed and biopsies were taken. The degree of atrophy was scored from 0 to 2 according to the Kimura-Takemoto classification. The degree of intestinal metaplasia was scored from 0 to 4 according to the location and the extent of the intestinal metaplasia. Results The correlation coefficient for atrophy between the endoscopic and histologic scores was 0.70 (95% CI: 0.52–0.81 p < .001) and for intestinal metaplasia, it was 0.75 (95% CI: 0.60–0.85; p < .001). For atrophic gastritis, an endoscopic score >1 correlated with OLGA stage III and IV with a sensitivity, specificity, positive predictive value, negative predictive value, and agreement of 88, 74, 75, 87, and 80.4%, respectively, and for intestinal metaplasia, an endoscopic score >1 correlated with high OLGIM stage III and IV with 100, 59, 69, 100, and 78.4%, respectively. Conclusions Endoscopic scoring for gastric atrophy and intestinal metaplasia using NBI-NFM likely correlates with histologic staging in Korea, a high-risk region for gastric cancer.

Association Between Degree of Gastritis and Malondialdehyde Level of Gastritis Patients at Adam Malik General Hospital Medan

Background: The main pathogenesis of gastritis is inflammation which process can not be separated from the role of free radicals. Malondialdehyde (MDA) is a free radical biomarker and which increases in gastritis patients. However, studies on MDA were generally performed on experimental animals or examined MDA in gastric mucosa. The aim of this study is to determine the association of histopathological degrees of gastritis (the degree of lymphocyte infiltration, neutrophil activity, atrophy, and intestinal metaplasia) with plasma MDA level.Method: Cross-sectional study of 40 consecutive gastritis patients who came to endoscopic unit of Adam Malik General Hospital Medan, from January to May 2017. Assessment for the severity of chronic inflammation, neutrophil activity, atrophy, and intestinal metaplasia refers to Updated Sydney System. Plasma MDA levels were examined using an HPLC MDA kit. Univariate and bivariate (Chi-square and fisher exact test) analysis were performed with SPSS version 22.Results: A total of 26 patients (65%) were men with an average age of 49.25 years. Lymphocyte infiltration was observed in 100% of specimens, neutrophil infiltration in 37.5%, atrophy in 22.5%, and intestinal metaplasia in 22.5%. There was a significant association between degree of lymphocyte infiltration with MDA level (p = 0.014; PR = 8.667; 95% CI: 1.52-89.52). There was a significant association between degree of neutrophil activity with high MDA level (p = 0.002; PR = 11.33; 95% CI: 2.64-48.74). There was a significant association between degree of atrophy with high level of MDA (p 0.001; PR = 14; 95% CI: 3.4–57.648). There was a significant association between degree of intestinal metaplasia with high MDA level (p = 0.001; PR = 12.5; 95% CI: 3.76-24).Conclusion: There were significant associations between degree of lymphocyte infiltration, neutrophil activity, atrophy, and intestinal metaplasia with high level of MDA.

Conifer Green Needle Complex in Patients with Precancerous Gastric Lesions: An Observational Pilot Study.

Objectives. Helicobacter pylori infection is common and can lead to precancerous gastric lesions. Standard antibiotic therapy has a failure rate of more than 25% from antibiotic resistance. The primary aim of this observational pilot study was to test the feasibility of a large-scale clinical trial of Conifer Green Needle Complex (CGNC) to treat precancerous gastric lesions. Secondary aims were to investigate H. pylori infection, stomach function, and histopathology of the gastric mucosa. Methods. A tablet form of CGNC (extracted from Pinus sylvestris and Picea abies (L) Karst) was prescribed to 26 patients with precancerous gastric lesions (two tablets, 100 mg CGNC/tablet, three times per day for six months). Another 24 patients received no treatment. Results. Compared with control patients, CGNC-treated patients showed total or partial regression (using the quantitative Rome III diagnostic criteria) of dyspeptic symptoms (92.3%, p < 0.0001), eradication of H. pylori infection (57.1%, p < 0.03), a reduction in endoscopic signs of gastritis (92.3%, p < 0.001), an increase of pepsinogen-pepsin in the gastric juice (57.7%, p < 0.05), and total regression or reduction in the degree of intestinal metaplasia (46.2%, p < 0.05) and lymphoplasmacytic infiltration (53.8%, p < 0.05). Conclusions. This study justifies a randomised-controlled trial with CGNC in patients with atrophic gastritis.

Adenocarcinomas at different positions at the gastro-oesophageal junction show distinct association with gastritis and gastric preneoplastic conditions.

Adenocarcinomas at the gastro-oesophageal junction (GOJ) are currently stratified by tumour location. This retrospective study examines the association of preneoplastic conditions and inflammation of the gastric mucosa with GOJ cancer at different locations and compares them with nonjunctional gastric cancers. A total of 520 patients with junctional and nonjunctional gastric cancer were assessed for the presence and degree of intestinal metaplasia, glandular atrophy and inflammation in the stomach. Histopathological data were complete for 428 patients (68.9% men, median age 67.7 years), including 172 patients with GOJ cancer (GOJ1: 1-5 cm proximal to the junction, GOJ2: 'true' junctional, GOJ3: 2-5 cm distal to the junction). Gastric inflammation and preneoplastic conditions were scored according to the updated Sydney classification and further stratified into respective operative link on gastritis assessment (OLGA) and operative link on gastritis assessment on intestinal metaplasia (OLGIM) stages. The prevalence and degree of gastric atrophy and intestinal metaplasia were significantly lower in GOJ1 than GOJ3 (P<0.01). Preneoplastic conditions in the stomach were similar in GOJ3 compared with nonjunctional gastric cancer. GOJ1 were almost exclusively (98.4%) of the intestinal type, whereas GOJ2 and GOJ3 were the diffuse type in 22.6 and 22.4% of the patients (P<0.001). Of all patients, only 8.5 and 12.7% presented with stage III/IV according to OLGA and OLGIM, respectively. However, data for OLGA and OLGIM staging were only available in 61.2 and 67.9% of patients, respectively. GOJ1 are less likely to be associated with gastric pathology compared with GOJ3 or nonjunctional gastric cancer. OLGA or OLGIM staging in patients with advanced gastro-oesophageal cancer seems to be of limited value.

Predictability of Gastric Intestinal Metaplasia by Mottled Patchy Erythema Seen on Endoscopy.

BackgroundIntestinal metaplasia (IM) is regarded as a premalignant lesion. However, endoscopic diagnosis of IM has been considered difficult. Using endoscopy, we found a unique pattern of erythema, “Mottled Patchy Erythema (MPE),” which includes severe IM. Helicobacter pylori (Hp) infection itself can cause erythema, which reflects histologic changes in the gastric mucosa. Therefore we enrolled Hp eradication patients to validate the relation between MPE and pathologic findings.MethodsWe enrolled patients with chronic gastritis who underwent successful Hp eradication at least 6 months before the study. We defined MPE as multiple flat or depressed erythematous lesions. When encountering MPE on endoscopy, we performed biopsy on both the MPE site and non-MPE site. The non-MPE site was defined as an adjacent mucosa located within 3 cm of the MPE site. All biopsy specimens were evaluated immunohistochemically for IM subtype using MUC2, MUC5AC, MUC6, CD10, and CDX2 stains. The degree of IM was defined according to the Updated Sydney System. The diagnostic accuracy of the MPE findings for pathologic IM was calculated. The relation between MPE and IM subtype was also assessed.ResultsA total of 102 patients were selected for the study. Of these, 55 (54%) patients had MPE. Biopsy specimens were taken from the MPE sites and non-MPE sites from these 55 patients. The IM percentages and median scores of IM were both significantly higher at the MPE sites (P < 0.001) than at the non-MPE sites. The sensitivity and specificity for MPE in the detection of histologic IM were 72.7% and 84.1%, respectively. No significant associations were observed in the expression of MUC2, MUC5AC, MUC6, CD10, and CDX2 between the MPE sites and non-MPE sites. There were no significant differences in the ratios (complete/incomplete) of IM subtypes between the two groups.ConclusionsMPE is a useful endoscopic finding to detect histologic IM without the use of chromoendoscopy and magnifying endoscopy. However, the IM subtype is difficult to identify. In the era of Hp eradication, MPE has the potential to become a predictive finding for the risk of gastric cancer.

Histopathological phenotypes of early gastric cancer and its background mucosa

Recent advances in endoscopic submucosal dissection (ESD) techniques contribute to endoscopic treatment of early gastric cancer (EGC). Recognition of chronic atrophic gastritis as the background is important for high-quality detection and diagnosis of EGC. But, relationships between EGC and atrophy of the background gastric mucosa caused by Helicobacter pylori are not well understood. The present study demonstrated histopathological phenotypes of EGC, as well as chronic atrophic gastritis as background mucosa of EGC. We evaluated mucosal heights, number of glands, and degree of intestinal metaplasia (IM) of the background gastric mucosa, using 81 cases of EGC resected by ESD. Gastric phenotype cancer cases showed IM of the background gastric mucosa less frequently, compared with intestinal phenotype cancer cases (score of IM, 1.15 vs. 1.65, P = 0.012). The average mucosal heights around EGC were lower in moderately to poorly differentiated adenocarcinoma cases than well differentiated adenocarcinoma cases (442.6 µm vs. 500.2 µm, P = 0.011). The mucosal atrophy indicated by average heights of background mucosa was low in the gastric phenotype cancer cases, compared with the intestinal phenotype cancercases (452.8 µm vs. 505.6 µm, P = 0.018). In the fundic gland area, the mucosal heights were low in the gastric phenotype cancer cases, compared with the intestinal phenotype cancer cases (413.2 µm vs. 495.5 µm, P = 0.015). Our results using EGC specimens indicated that gastric phenotype cancer and moderately to poorly differentiated adenocarcinoma had atrophic background mucosa with lower mucosal heights and less IM. The atrophic gastric mucosa with less IM is thought to play an important role in gastric carcinogenesis, especially tumoriogenesis of gastricphenotype cancer.

W1876 Stool Protein Markers for Colorectal Cancer: Identification of High-Abundance Candidates By Mass Spectroscopy

Background and Aim: Altered expression of multidrug resistance 1 (MDR1) contributes to various cancers and its disease progression. DNA methylation is reported to present in various non-cancerous tissue as age-related phenomenon, suggesting that it occurs early in the process of tumorgenesis. We investigated the effect of MDR 1 gene promoter methylation on carcinogenesis in the stomach. Methods: In study A, we estimated the methylation ratio (MR) of the MDR1 gene promoter in both antral noncancerous mucosa and cancer lesions in 83 patients with gastric cancer (GC). In study B, we also estimated the MR in noncancerous gastric mucosa in 127 patients with GC and 82 cancer free (non-GC) subjects. Degree of histological chronic gastritis was scored according to updated Sydney systems in 200 subjects. We employed methylation-specific PCR method. Results: In the study A, MR of cancer lesions (31.3±20.5) was significantly higher than that of non noncancerous mucosa (20.9±31.3, p= 0.0004). MR was especially higher in Lauren's intestinal cancer (p<0.0001). Higher MR was also observed in more advanced stage (p=0.005), and lymph vessel invasion positive cases (p=0.002). In the study B, a significant association was found between higher methylation ratio (MR) and occurrence of GC (GC vs. non GC; 21.3±24.8 vs.10.3±14.3, H. pylori infection adjusted p = 0.001). Higher MR was also associated with occurrence of GC in both H. pylori positive (p=0.006) and negative (p=0.03) subjects. Furthermore, higher MR was closely associated with H. pylori infection status (p<0.0001), and degree of intestinal metaplasia (p=0.0008) Conclusion: The promotermethylation ofMDR1 have a significant role in carcinogenesis and tumor progression in the stomach. Furthermore, promoter methylation status of MDR1 gene in non-cancerous gastric mucosa also seems to be associated with H. pylori infection, severity of intestinal metaplasia, and GC occurrence.

Study of clinicopathological factors associated with the occurrence of synchronous multiple gastric carcinomas

Multiple gastric carcinomas often arise in gastric mucosa with chronic gastritis, particularly severe intestinal metaplasia. In regard to such characteristics, several clinicopathological risk factors for multiple carcinomas have been reported, but no clinically useful criteria are available at present for assessing the onset of multiple gastric carcinomas. If the risk for multiple gastric carcinomas could be accurately assessed, efficient and accurate surveillance could be performed following minimally invasive therapies. In the present study, we investigated clinicopathological differences between 94 cases of multiple early gastric carcinomas and 285 cases of solitary early gastric carcinoma. We tested 379 specimens of gastric carcinomas that had been surgically resected at the Department of General and Gastroenterological Surgery of Osaka Medical College, Japan, from April 1999 to December 2006. Univariate analysis of clinicopathological factors in the present study showed that multiple gastric carcinomas were significantly correlated to old age (> or =65 years), well- and moderately differentiated histological type, mucin phenotype (intestinal type), distribution of atrophic mucosa in the stomach (severe), degree of intestinal metaplasia in the surrounding mucosa (severe), and heterotopic glandular cysts. Multivariate analysis using the stepwise method identified age (> or =65 years) and degree of intestinal metaplasia in the surrounding mucosa (severe) as significant independent risk factors for multiple gastric carcinomas. While other studies have shown risk factors for multiple gastric carcinomas, the present study is unique in showing risk assessment criteria based on a combination of risk factors for multiple gastric carcinomas.

The combined presence of H pylori infection and gastro-oesophageal reflux disease leads to an up-regulation of CDX2 gene expression in antrum and cardia

Background:CDX2 is an epithelial transcription factor that regulates intestinal differentiation and is involved in the development of intestinal metaplasia (IM).Aim:To analyse the expression of CDX2 in the gastric mucosa in...

Association of polymorphism of the p22PHOX component of NADPH oxidase in gastroduodenal diseases in Japan

Objective. Superoxide has been implicated in the pathogenesis of Helicobacter pylori-related diseases through inflammation. NADPH oxidase, a major source of superoxide generation, plays a critical role in H. pylori-related gastric inflammation. The aim of this study was to clarify the effect of the p22PHOX C242T polymorphism, an essential component of NADPH oxidase in the risk of gastroduodenal diseases, on the severity of H. pylori-induced gastritis in a Japanese population. Material and methods. The study comprised 436 patients attending the Endoscopy Center of Fujita Health University Hospital. The p22PHOX C242T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Gastritis scores of antral gastric mucosa were assessed according to the updated Sydney system. Results. The 436 patients represented 106 gastric ulcers (24.3%), 48 duodenal ulcers (11.0%), and 282 non-ulcer subjects (64.7%). No association was found between p22PHOX polymorphism and the risk of ulcer diseases compared to non-ulcer subjects. However, among H. pylori-positive subjects, the degree of intestinal metaplasia tended to be lower in 242T carriers aged more than 60 years (p=0.0488). The same allele also decreased the risk of developing a more severe intestinal metaplasia in H. pylori-positive female subjects (p=0.0441). Conclusions. Our data suggest that the p22PHOX 242T allele is associated with a reduced risk of developing a more severe intestinal metaplasia in subjects older than 60 years of age and in female subjects with H. pylori infection.

Effect of RANTES Promoter Genotype on the Severity of Intestinal Metaplasia in Helicobacter pylori-Infected Japanese Subjects

A complex interaction of host genetic and environmental factors may be relevant in the development of Helicobacter pylori (H. pylori)-related gastro-duodenal diseases. RANTES is a potent chemoattractant peptide for memory T lymphocytes and eosinophils, and has been shown to be enhanced in H. pylori-infected gastric mucosa. We aimed to clarify the effect of RANTES functional promoter polymorphism on the risk of gastro-duodenal diseases in a Japanese population. Four hundred and eighty-three subjects, comprising 106 gastric ulcer, 52 duodenal ulcer, and 325 non-ulcer subjects, were included in this study. Restriction fragment length polymorphism (RFLP) analysis was performed for polymorphisms at -28 C/G in the RANTES gene promoter region. Gastritis scores of antral gastric mucosa were assessed according to the updated Sydney system. There were no significant differences in the RANTES promoter genotype distributions among non-ulcer subjects, ulcer patients, and gastric and duodenal ulcers. However, the degree of intestinal metaplasia was significantly lower among G carriers in H. pylori-infected subjects aged 60 years or older (C/C vs. G carriers; 1.28 +/- 1.02 vs. 0.83 +/- 0.89, P = 0.0357). In addition, we also found that the same genotype held a lower risk of more severe intestinal metaplasia in H. pylori-infected female subjects (C/C vs. G carriers; 0.91 +/- 1.03 vs. 0.41 +/- 0.73, P = 0.0443). The polymorphism of RANTES promoter is not associated with the susceptibility to peptic ulcer diseases, but the -28 G carrier is associated with a reduced risk of developing more severe intestinal metaplasia in H. pylori-positive subjects aged 60 years and older and in female subjects.

GASTRIC CANCER DETECTED AFTER HELICOBACTER PYLORI ERADICATION

Background: Helicobacter pylori is associated with progression to gastric cancer. However, it is still unclear whether eradication therapy can prevent the development of gastric cancer.Methods: Subjects were 242 patients in whom success in eradication of Helicobacter pylori had been continuous for more than 3 years. Clinical, endoscopic and histological findings were compared retrospectively between those who developed gastric cancer (cancer group) and those who did not (non‐cancer group). Clinical features of each cancer case were also evaluated.Results: Gastric cancer was found in six of the 242 subjects (2.5%) during a mean follow‐up period of 4.6 years (range: 3.0–7.0). The mean age of the cancer group tended to be higher than that of the non‐cancer group. Endoscopy revealed a more severe grade of gastric corpus atrophy in the cancer group, and histological findings showed that the degree of intestinal metaplasia in the upper corpus was higher in the cancer group. Four of the six cancers were located in the gastric antrum. All were early cancers and five were of 0‐IIc type endoscopically. All were intestinal type histologically.Conclusions: Gastric cancer was discovered at a rate of 2.5% during the mean follow‐up period of 4.6 years after H. pylori eradication. Careful endoscopic follow up is necessary even after successful eradication, especially in cases characterized by an endoscopically high grade of gastric atrophy and pathologically severe intestinal metaplasia at the upper corpus.

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Mucin phenotype and microsatellite instability in early multiple gastric cancers.

Clinicopathologically, multiple gastric cancers (MGCs) are reported to involve predominantly intestinal-type adenocarcinoma and frequently to be associated with severe intestinal metaplasia. However, there are few reports concerning the characteristic biomarkers of early MGCs. The aim of our study was to identify the cellular lineage defined by mucin phenotypes and the relationships among mucin phenotypes, background mucosa and microsatellite instability (MSI) of early MGCs. We examined mucin phenotypes of 63 surgically resected carcinomas from 25 patients with early MGCs and 39 early solitary gastric cancers (SGCs) by immunohistochemical analysis using a panel of monoclonal antibodies. MSI and the degree of intestinal metaplasia (IM) on the background mucosa were also examined. In early MGCs, the incidence of cancer exhibiting the gastric phenotype (G-type) was 59% (37 of 63 cancers), which was higher than that in early SGCs (23%, 9 of 39 cancers). There was a significant difference between the distributions of mucin phenotypes in early MGCs and early SGCs (p = 0.001). Whereas half of the G-type cancers in early MGCs were related to severe IM, none of the G-type cancers in early SGCs were related to severe IM. In the early MGCs, MSI was observed in 21 of 63 cancers (33.3%). In contrast, MSI was observed in only 3 of the 39 (7.7%) early SGCs, indicating a significant difference between these 2 groups (p < 0.01). Our results suggest that the characteristic features of early MGCs are the gastric mucin dominant phenotype and high frequency of MSI.

Helicobacter pylori eradication dramatically improves inflammation in the gastric cardia

OBJECTIVES: Inflammation of the gastric cardia, i.e., “carditis,” has been associated with Helicobacter pylori ( H. pylori) infection; however, some investigators believe carditis to be a histological marker for gastroesophageal reflux disease. The aim of this study was to investigate the role of H. pylori eradication on the grade of carditis scored according to the updated Sydney classification. METHODS: Consecutive patients presenting for upper endoscopy underwent systematic gastric biopsies (eight antral, 12 corpus, and four cardia). Patients with H. pylori infection and carditis were identified and followed prospectively before and after H. pylori treatment. At pretreatment and, on average, 2 yr after eradication of H. pylori, the degree of inflammation in the gastric cardia and H. pylori status were blindly assessed by a single pathologist. RESULTS: A total of 31 patients with H. pylori infection and carditis were identified. The mean age was 70 yr (range: 37–81 yr); all were male. Four were African-American and 27 were Caucasian. All patients were treated with standard anti- H. pylori therapy, including a proton pump inhibitor in combination with two antibiotics for 2 wk. Eradication of H. pylori was successful in 23 patients (group I), whereas eight patients had persistent infection (group II). Patients were followed after eradication therapy for a mean of 23.2 months (range: 6–48 months). After eradication therapy, there was a significant decrease ( p < 0.0001) in the carditis scores (activity and inflammation scores) in group I, whereas the scores remained unchanged in group II patients. In both groups, there were no significant changes in the degree of intestinal metaplasia or atrophy. There were four patients with intestinal metaplasia, and one with atrophy. CONCLUSIONS: There is a dramatic improvement in the degree of inflammation and activity scores in the gastric cardia of patients with successful H. pylori eradication compared to those with persistent infection. By fulfilling one of Koch’s postulates ( i.e., improvement in the disease after cure of the possible etiological organism), these data support H. pylori as being the etiological agent for carditis in this group of patients.

Helicobacter pylori eradication dramatically improves inflammation in the gastric cardia

Inflammation of the gastric cardia, i.e., "carditis," has been associated with Helicobacter pylori (H. pylori) infection; however, some investigators believe carditis to be a histological marker for gastroesophageal reflux disease. The aim of this study was to investigate the role of H. pylori eradication on the grade of carditis scored according to the updated Sydney classification. Consecutive patients presenting for upper endoscopy underwent systematic gastric biopsies (eight antral, 12 corpus, and four cardia). Patients with H. pylori infection and carditis were identified and followed prospectively before and after H. pylori treatment. At pretreatment and, on average, 2 yr after eradication of H. pylori, the degree of inflammation in the gastric cardia and H. pylori status were blindly assessed by a single pathologist. A total of 31 patients with H. pylori infection and carditis were identified. The mean age was 70 yr (range: 37-81 yr); all were male. Four were African-American and 27 were Caucasian. All patients were treated with standard anti-H. pylori therapy, including a proton pump inhibitor in combination with two antibiotics for 2 wk. Eradication of H. pylori was successful in 23 patients (group I), whereas eight patients had persistent infection (group II). Patients were followed after eradication therapy for a mean of 23.2 months (range: 6-48 months). After eradication therapy, there was a significant decrease (p < 0.0001) in the carditis scores (activity and inflammation scores) in group I, whereas the scores remained unchanged in group II patients. In both groups, there were no significant changes in the degree of intestinal metaplasia or atrophy. There were four patients with intestinal metaplasia, and one with atrophy. There is a dramatic improvement in the degree of inflammation and activity scores in the gastric cardia of patients with successful H. pylori eradication compared to those with persistent infection. By fulfilling one of Koch's postulates (i.e., improvement in the disease after cure of the possible etiological organism), these data support H. pylori as being the etiological agent for carditis in this group of patients.

Minute gastric carcinoma of differentiated type with special reference to the significance of intestinal metaplasia, proliferative zone, and p53 protein during tumor development

BACKGROUND The differentiated type of minute gastric carcinoma (MGC), measuring less than 5 mm in greatest dimension, has been considered to represent the incipient phase of gastric carcinoma. To determine the clinicopathologic features of MGCs, the authors examined tissues from MGCs with a view to clarifying their histopathologic diversity. The immunohistochemistry of these tissues was determined using monoclonal antibody against p53 and Ki-67, and their mucin-histochemical types were determined with reference to the presence of intestinal metaplasia (IM) within their surrounding mucosa. METHODS One hundred three specimens were obtained from 93 patients with MGCs. Each lesion was evaluated both macroscopically and histologically, and the degree of IM was assessed. All sections were examined mucin-histochemically with Con A, GOS, and HID-AB, and stained with commercially available monoclonal antibodies, PAb 1801 and Ki-67. Additional nonminute carcinomas present within the same stomachs were used as controls. RESULTS Macroscopically, most lesions were depressed. IM was noted in the surrounding mucosa of 85 MGCs (82.5%). Immunohistochemically, 25 MGCs (24.2%) showed p53 overexpression, although the rate of p53 overexpression was increased to 34.6% in other nonminute carcinomas from the same stomachs. Twenty-four MGCs were associated with a proliferative zone, demonstrated by Ki-67 positive cells. Statistically significant differences in the rate of p53 overexpression were observed between MGCs with a proliferative zone and those without. Mucin phenotypes of MGCs tended to imitate their own surrounding mucosa. CONCLUSIONS The MGCs, which represent the incipient phase of early gastric carcinoma, have various histologic, immunohistochemical, and mucin-histochemical features. It would seem that p53 expression is more closely related to the progression of MGCs than to their carcinogenesis. Cancer 1999;85:1719–29. © 1999 American Cancer Society.

Minute gastric carcinoma of differentiated type with special reference to the significance of intestinal metaplasia, proliferative zone, and p53 protein during tumor development

The differentiated type of minute gastric carcinoma (MGC), measuring less than 5 mm in greatest dimension, has been considered to represent the incipient phase of gastric carcinoma. To determine the clinicopathologic features of MGCs, the authors examined tissues from MGCs with a view to clarifying their histopathologic diversity. The immunohistochemistry of these tissues was determined using monoclonal antibody against p53 and Ki-67, and their mucin-histochemical types were determined with reference to the presence of intestinal metaplasia (IM) within their surrounding mucosa. One hundred three specimens were obtained from 93 patients with MGCs. Each lesion was evaluated both macroscopically and histologically, and the degree of IM was assessed. All sections were examined mucin-histochemically with Con A, GOS, and HID-AB, and stained with commercially available monoclonal antibodies, PAb 1801 and Ki-67. Additional nonminute carcinomas present within the same stomachs were used as controls. Macroscopically, most lesions were depressed. IM was noted in the surrounding mucosa of 85 MGCs (82.5%). Immunohistochemically, 25 MGCs (24.2%) showed p53 overexpression, although the rate of p53 overexpression was increased to 34.6% in other nonminute carcinomas from the same stomachs. Twenty-four MGCs were associated with a proliferative zone, demonstrated by Ki-67 positive cells. Statistically significant differences in the rate of p53 overexpression were observed between MGCs with a proliferative zone and those without. Mucin phenotypes of MGCs tended to imitate their own surrounding mucosa. The MGCs, which represent the incipient phase of early gastric carcinoma, have various histologic, immunohistochemical, and mucin-histochemical features. It would seem that p53 expression is more closely related to the progression of MGCs than to their carcinogenesis.

Comparison of different permeability probes in patients with spondylarthropathy and noninflammatory rheumatic disease: What is the effect of NSAIDs?

relates to the presence of CagA. The evolution of 1-1. pylori related gastritis was studied in relation to cagA and to duration of follow-up, in patients with either persistent or cured H. pylori infection. Dyspeptic patients entered the study starting in 1984. H. pylori infection was assessed by culture and histopathology of antral biopsies. The grading of activity of gastritis, superficial epithelial damag e (SED), atrophy and intestinal metaplasia (IM) was based on the updated Sydney classification. CagA status was determined by specific serum IgG antibodies. H. pylori eradication was attempted with bismuth-, or ppi-antibiotic combination therapies. Results of 265 patients were available for analysis. The median follow up was 5.3 years (range 1.1-12.5). Group I consisted of 124 patients with persisting H. pylori infection. Group II consisted of 141 patients in whom H. pylori eradication was achieved. CagA results were available in 185/265 patients (94 of group I; 91 of group II) of whom 140 (76%) were infected with a CagA ÷ strain. Pretreatment degrees of activity, SED, atrophy and IM were similar (ns) in group I and II. Higher degree of activity and SED was found in CagA+ infected patients (p < 0.0001). The degree of activity, SED, atrophy and IM remained unchanged over the years in group I. After successful H. pylori eradication, the degree of activity and SED improved significantly (p < 0.001), irrespective of the CagA status. The degree of atrophy improved from 2.2 to 1.2 (p < 0.001) in CagA+infected patients, however, the degree of atrophy remained unaffected in CagA-neg infected patients (from 1.8-1.6; ns). The degree of IM remained unchanged after successful H. pylori eradication, irrespective of the CagA status. Mean degrees of gastritis in group I and II, after a follow-up period less than 4 years or more than 4 years, were similar (ns). In conclusion, atrophy is partially reversible in CagA+infected patients, but IM remains unchanged. In CagA-neg H. pylori infection, atrophy and IM appeared irreversible. The length of follow-up in this cohort did not influence the observed degrees of activity, SED, atrophy and IM. Whether partial reversibility of atrophy will lead to reduction in cancer risk requires further prolonged observation.