Case of early gastric cancer with nodular gastritis

A case of depressed early gastric cancer with nodular gastritis is described. A 47‐year‐old Japanese man was referred to our hospital and admitted for surgical treatment of gastric cancer. Barium upper gastrointestinal study and endoscopy examination showed a 4.5 × 3.0 cm depressed lesion with a deep central ulceration in the anterior wall of the lower corpus. An unusual miliary pattern resembling ‘goose flesh’ was observed endoscopically in the antrum. Biopsy specimens from the tumor showed poorly differentiated adenocarcinoma, and specimens from the antrum showed many lymphoid follicles with a germinal center. Immunoglobulin G antibody and histological tests (Giemsa stain) for Helicobacter pylori were both positive. Early gastric cancer with nodular gastritis was diagnosed and a subtotal gastrectomy was performed. Histological examination of the resected specimen showed a stage I tumor infiltrating a poorly differentiated adenocarcinoma with a depressed lesion in the corpus (type 0 IIc + III) and nodular gastritis in the antrum. The patient is doing well 1 year after surgery.     

Advanced gastric cancer associated with nodular gastritis in a young patient

A 20-year-old female underwent an endoscopy for epigastralgia that revealed many small, elevated nodules in the antrum that were diagnosed as nodular gastritis. The endoscopy also showed an ulcerative lesion with an uneven round wall at the greater curvature of the middle corpus. Biopsy of the ulcerative lesion yielded a diagnosis of poorly differentiated adenocarcinoma. A distal gastrectomy was performed on the basis of a diagnosis of gastric cancer associated with nodular gastritis. The intraoperative findings revealed serosal invasion of the gastric cancer and the patient tested positive for peritoneal cytology. The pathological findings revealed poorly differentiated adenocarcinoma showing invasive growth with fibrosis on the corpus and large and superficial lymphoid follicles on the miliary nodules at the antrum. The patient was positive for Helicobacter pylori infection by both the serum Helicobacter pylori antibody and histopathological findings.     

A CASE OF DIFFUSE‐TYPE EARLY GASTRIC CANCER WITH NODULAR GASTRITIS

A 39‐year‐old woman was referred to Osaka Police Hospital and admitted for surgical treatment of gastric cancer. Barium upper gastrointestinal study and endoscopic examination showed a 3.0 × 3.0 cm depressed lesion in the greater curvature of the middle corpus. An unusual miliary pattern resembling ‘goose flesh’ was observed endoscopically in the antrum. Biopsy specimens from the tumor showed poorly differentiated adenocarcinoma, and specimens from the antrum showed many lymphoid follicles with a germinal center. Rapid urease test and histological tests (Giemsa stain) for Helicobacter pylori were both positive. Early gastric cancer with nodular gastritis (NG) was diagnosed and a partial gastrectomy was performed. Histological examination of the resected specimen showed a stage I tumor consisting mainly of signet‐ring cell carcinoma restricted to the mucosa. Postoperatively H. pylori eradication therapy was performed and proved to be successful. One year after eradication therapy, endoscopy with biopsy showed no recurrence of gastric cancer and the remarkable regression of antral NG.     

NODULAR GASTRITIS AND GASTRIC CANCER

Nodular gastritis is defined as antral gastritis usually characterized endoscopically by a miliary pattern resembling gooseflesh and pathologically by prominent lymphoid follicles and infiltration of mononuclear cells. This physiological phenomenon was once considered particular to young women. Recent studies have shown that nodular gastritis is strongly associated with Helicobacter pylori infection and may be associated with gastric cancer. Reported cases of gastric cancer with nodular gastritis showed some features in common: all gastric cancers were diagnosed histologically as the diffuse‐type, and all were located in the corpus with Helicobacter pylori infection. Because nodular gastritis may be a risk factor for diffuse‐type gastric cancer, Helicobacter pylori may need to be eradicated to prevent gastric cancer in patients with nodular gastritis.     

Gastric Mucosa Epithelial Cell Kinetics Are Differentiated by Anatomic Site and Helicobacter Pylori Infection

Changes in epithelial cell turnover related to Helicobacter pylori infection may contribute to gastric cancer development. The response of different anatomic sites of the gastric mucosa to H. pylori is not known. We studied apoptosis and cell proliferation at the grater and lesser curvature of the antrum and corpus, the fundus, and the cardia from 9 H. pylori gastritis patients and 11 H. pylori-negative controls with normal histology. Proliferation was highest at the major curve of the antrum and lowest at the fundus, and apoptosis was highest at the cardia and lowest at the major curve of the antrum in both H. pylori gastritis and normal mucosa. Proliferation was significantly higher at all anatomic sites, while apoptosis was significantly lower only at the major and lesser curve of the corpus in H. pylori gastritis compared with normal controls. Our data suggest that gastric mucosa epithelial cell kinetics is differentiated by the anatomic site and H. pylori infection.     

Advanced gastric cancer of the antrum: anatomic-functional correlation between chief cell mass and serum pepsinogen I.

Chief cell mass and type I serum pepsinogen (PGI) were calculated in 19 advanced antral gastric cancer of intestinal type. Comparisons were also made with parietal cell mass and acid secretion. In gastric cancer of the antrum there is a significant decrease of the chief cell mass and of serum pepsinogen I. The patients were subdivided according to the histological findings of the fundic mucosa. In cases of antral gastric cancer with superficial fundic gastritis there is normozymogenism with hyperpepsinogenemy; with preatrophic fundic gastritis there is hypozymogenism with normopepsinogenemy; with atrophic fundic gastritis there is hypozymogenism with hypopepsinogenemy. Similar behavior of the chief cell mass between antral gastric cancer and fundic atrophic gastritis without cancer has become recognized and while the validity of PGI as a marker of fundic atrophic gastritis has emerged it does not allow discrimination between atrophic fundic gastritis and atrophic fundic gastritis associated with gastric cancer of the antrum.     

Advanced gastric cancer of the antrum: Anatomic-functional correlation between chief cell mass and serum pepsinogen I

Chief cell mass and type I serum pepsinogen (PGI) were calculated in 19 advanced antral gastric cancer of intestinal type. Comparisons were also made with parietal cell mass and acid secretion. In gastric cancer of the antrum there is a significant decrease of the chief cell mass and of serum pepsinogen I. The patients were subdivided according to the histological findings of the fundic mucosa. In cases of antral gastric cancer with superficial fundic gastritis there is normozymogenism with hyperpepsinogenemy; with preatrophic fundic gastritis there is hypozymogenism with normopepsinogenemy; with atrophic fundic gastritis there is hypozymogenism with hypopepsinogenemy. Similar behavior of the chief cell mass between antral gastric cancer and fundic atrophic gastritis without cancer has become recognized and while the validity of PGI as a marker of fundic atrophic gastritis has emerged it does not allow discrimination between atrophic fundic gastritis and atrophic fundic gastritis associated with gastric cancer of the antrum.     

Nodular gastritis in adults is caused by Helicobacter pylori infection

A close relationship exists between nodular gastritis and Helicobacter pylori infection in children. The pathogenesis and optimal management of nodular gastritis in adults, however, are unclear. This study describes the clinicopathologic features of nodular gastritis in adults and correlates treatment with outcome. Of 97,262 adult patients who underwent endoscopy, 187 (0.19%) were diagnosed with nodular gastritis, 151 (81%) of whom had dyspepsia. Nodular gastritis predominantly affects young women (49 men and 138 women, mean age, 32.6 years). All 134 patients tested for Helicobacter pylori infection were infected, and 65/66 (98%) had inflammation of both the antrum and the corpus. Twenty-five (13%) had associated lesions (peptic ulcers or cancer). Dyspepsia improved after eradication of Helicobacter pylori infection, but did not improve spontaneously. Nodular gastritis in adults is caused by Helicobacter pylori infection and shows a predilection for females and young adults. Helicobacter pylori eradication decreases symptoms and reduces the risk of peptic ulcers and possibly gastric cancer.     

Correlation between serum pepsinogen levels and gastric mucosal histological findings before and after Helicobacter pylori eradication therapy

Background: Helicobacter pylori causes chronic gastritis and is also associated with many other gastrointestinal diseases. The incidence of gastric cancer is thought to vary according to the degree and topography of chronic gastritis. Histological findings of specimens obtained at endoscopy are therefore important. In the present study, we investigated the correlation between these histological findings and serum pepsinogen (PG) levels. Methods: Helicobacter pylori eradication therapy was conducted in 100 H. pylori‐positive patients. Endoscopies were performed prior to, and 2 months after, eradication therapy; gastric mucosal biopsies were taken from the antrum and corpus. Helicobacter pylori infection was diagnosed using the rapid urease test, culture and histology. Using the Updated Sydney System, histological findings of inflammation, activity, atrophy and intestinal metaplasia were each graded. Blood was taken on the same two occasions for determination of serum levels of PG I and II. Results: Levels of PG I were highest in association with antrum‐predominant gastritis (APG), followed in order by pangastritis (PAN) and corpus‐predominant gastritis (CPG), with a significant difference between APG and CPG. No correlations were seen between PG II levels and gastritis topography. Examination of the relationship between PG levels and histological findings revealed significant correlations between PG I levels after eradication atrophy and intestinal metaplasia in the gastric corpus. No significant correlations were seen between PG II levels and before or after eradication histological findings. Conclusion: Our results indicate that serum PG levels may be a useful indicator of before‐eradication gastritis topography and after‐eradication gastric atrophy in the gastric corpus.     

Coexistence of multifocal gastric adenocarcinoma with signet-ring cell morphology and a gastrointestinal stromal tumour in a stomach with hp-associated gastritis

A 79-year-old man was admitted because of anemia during marcumar therapy with suspected bleeding in the gastrointestinal tract. Endoscopy revealed a large mutifocal poorly differentiated gastric signet ring cell adenocarcinoma. After staging by the usual oesophagogastroduodenoscopic method, a total D 2 gastrectomy was performed. In the pathological resection specimen of the stomach, a multifocal poorly differentiated signet ring cell adenocarcinoma, infiltrating the submucosa (so called early cancer of sm-type) and an incidental gastroinstinal stromal tumour, 0.8 cm in diameter, was diagnosed. This is the first case report of the synchronous occurrence of a multifocal poorly differentiated gastric adenocarcinoma with signet-ring cell morphology (diffuse type according to the Lauren classification) and a GIST incidentally within a stomach with Hp-associated gastritis.     

Helicobacter pylori gastritis of the gastric cancer phenotype in relatives of gastric carcinoma patients.

OBJECTIVE: Infection with Helicobacter pylori is associated with gastric cancer. However, a hereditary risk of gastric cancer has also been reported. Hence, we decided to evaluate H. pylori gastritis in relatives of gastric cancer patients in comparison with matched controls. DESIGN: Case-controlled study. METHODS: A total of 237 patients with merely H. pylori gastritis (i.e. not associated with either peptic ulcer or gastric malignancy), and either first-degree (93.7%) or second-degree (6.3%) relatives with gastric cancer, were age- and sex-matched with 237 patients with H. pylori gastritis unassociated with a family history of gastric cancer. From each patient, antral and corpus biopsy specimens were obtained and investigated for degree (lymphocyte/plasma cell infiltration) and activity (polymorph infiltration) of gastritis (score: 0-4). Intestinal metaplasia was recorded as present or absent. RESULTS: The results show that relatives of gastric cancer patients have a significantly greater expression of gastritis due to a higher grade of gastritis in the antrum and corpus (P < 0.0001) and a greater activity of gastritis in the corpus (P < 0.0001). Intestinal metaplasia occurs more often in relatives of gastric cancer patients (antrum: P < 0.0001; corpus: P = 0.0237). CONCLUSION: Since the grade of H. pylori gastritis in relatives of gastric cancer patients is significantly higher than in controls, there appears to be a genetic susceptibility influencing the expression of H. pylori gastritis.     

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

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

Topography of chronic active gastritis in Helicobacter pylori-positive Asian populations: age-, gender-, and endoscopic diagnosis-matched study

Background The incidence and mortality of gastric cancer is high among Japanese and Chinese populations but extremely low in Thailand and low in Vietnam. The aim of this study was to compare the degree of corpus-predominant gastritis, which is considered to be one of risk factors of gastric cancer, in Helicobacter pylori-positive Asian adult populations.Methods H. pylori-positive Chinese (Beijing and Fuzhou), Thai, and Vietnamese patients were paired with Japanese patients by age, gender, and endoscopic diagnosis to compare the ratio of corpus gastritis to antrum gastritis (C/A ratio) (105, 85, 195, and 154 pairs, respectively).Results The Japanese C/A ratio was significantly higher than that in other groups. Corpus-predominant gastritis (C/A ratio > 1.00) was characteristic in aged Japanese and Chinese (Fuzhou), but Chinese (Beijing), Thai, and Vietnamese were antrum predominant (C/A ratio < 1.00) in every age group except for the Vietnamese over-70 group. There was a similarity between degree of H. pylori colonization and neutrophil activity score.Conclusions Corpus-predominant gastritis was found in aged Japanese and Chinese (Fuzhou) and antrum-predominant gastritis was found in Chinese (Beijing), Thai, and Vietnamese patients. These results correlate with the low incidence of gastric cancer in Thai and Vietnamese populations.     

Proton pump inhibitors and H. pylori infection: Why the concern?

Summary Proton pump inhibitor therapy, even on a short-term basis, is associated with a decrease in antral gastritis and an increase in gastritis of the body. On a long-term basis, some series show the development of atrophic gastritis and some show none or hardly any. All studies fail to show or to report any significant increase in the prevalence of intestinal metaplasia with long-term PPI therapy. If one wants to determine whether PPIs cause atrophic gastritis with intestinal metaplasia, then the angularis primarily and the gastric antrum secondarily need to be studied because that is where most IM resides in the intestinal types of cancer. Instead of focusing on the angularis an antrum, the studies have evaluated biopsies from the gastric body, the least likely spot to be intestinalized in association with the intestinal type of gastric cancer. H. pylori is associated with both intestinal and diffuse types of gastric cancer. Obtaining an answer to the question of whether PPI therapy or any other type of therap increases gastric cancer risk in H. pylori-positive patients will require epidemiologic studies in which cancer is the end point. Intermediate theoretic markers are not available for diffuse cancers. If intermediate markers are used for the intestinal type of gastric cancer, then atrophic gastritis with intestinal metaplasia might provide some insight on theoretical grounds. However, the published long-term studies to date have not addressed that question because of where they have focused the biopsy sampling, and/or because of failure to report data on intestinal metaplasia.     

Comparative Classification and Grading of Helicobacter pylori Gastritis in Patients with Gastric Cancer and Patients with Functional Dyspepsia

Background: It has previously been shown that corpus-dominant grade and activity of Helicobacter pylori gastritis in combination with intestinal metaplasia in the antrum or corpus are risk markers for the development of stomach cancer. If one point is scored for each of these three parameters, a gastric cancer risk index is obtained that permits prediction of the risk of gastric cancer developing on the soil of H. pylori gastritis. The aim of the present study was to evaluate the accuracy of the gastric cancer risk index based on a large number of patients compared with dyspeptic controls. Methods: In 415 biopsied patients with gastric carcinoma, biopsy specimens taken from the antrum and corpus were investigated retrospectively. From this group of patients, 244 patients positive for H. pylori were compared with 244 sex- and age-matched H. pylori -infected patients with functional dyspepsia. Results: H. pylori gastritis was detected in 395 carcinoma patients (95.2%). The 244 sex- and age-matched patients significantly more frequently had corpus-dominant H. pylori gastritis (compared with NUD controls). The incidence of intestinal metaplasia was also significantly increased. For a gastric cancer risk index score of 3 points (i.e. corpus pronounced grade and activity of gastritis, and intestinal metaplasia in antrum or corpus), a sensitivity of 93% and a specificity of 85% for the presence of gastric carcinoma can be calculated. Conclusion: Using the proposed risk index, the topographic grading of H. pylori gastritis in the antrum and corpus enables the diagnosis of a 'risk gastritis' to be made.     

XRCC1 downregulated through promoter hypermethylation is involved in human gastric carcinogenesis

OBJECTIVE: To analyze the expression and aberrant methylation of X-ray repair cross-complementing gene 1 (XRCC1) in gastric carcinogenesis, and identify the molecular mechanism of gastric carcinogenesis. METHODS: The method based on methyl binding domain protein (MBD) immuno-precipitation and promoter microarray was employed to screen the gastric cancer-related methylation-sensitive gene. An immunohistochemistry assay was applied to detect the protein expression of XRCC1 in the multistep progression of gastric carcinogenesis. The mRNA expression of XRCC1 was determined by real-time PCR in tumor tissues and their corresponding non-tumorous tissues. The methylation status and Arg194Trp and Arg399Gln polymorphisms of XRCC1 in gastric cancer and gastritis tissues were analyzed by methylation-specific PCR, bisulfite genomic sequencing and direct DNA sequencing, respectively. RESULTS: Promoter microarray screening and identification suggested that XRCC1 was a methylation-sensitive gene. Immunochemistry results showed that XRCC1 protein expression gradually decreased with progression of gastric mucosal lesions (P < 0.05). The positive rate of XRCC1 in patients with well/moderately differentiated gastric cancer was significantly higher than patients with poorly differentiated gastric cancer (P < 0.05). The mRNA expression of XRCC1 in gastric cancer tissues was significantly lower than that in the non-tumorous tissues (P < 0.05). Meanwhile, XRCC1 methylation in gastric cancer tissues was more frequent than that in the gastritis tissues (P < 0.05), and the downregulation of XRCC1 expression was relevant to methylation (P < 0.05). CONCLUSION: The expression of XRCC1 is downregulated in gastric carcinogenesis, and promoter hypermethylation may be one of the mechanisms contributing to its downregulation.     

Epithelial cell turnover in relation to ongoing damage of the gastric mucosa in patients with early gastric cancer: increase of cell proliferation in paramalignant lesions

Background Gastric cancer is typically an end result of Helicobacter pylori-associated chronic gastritis. The pathogenesis is thought to involve effects on gastric mucosal epithelial cell turnover. In this study, we aimed to compare apoptosis and proliferation in the noncancer-containing mucosa of H. pylori-positive patients with early gastric cancer with these phenomena in H. pylori-positive controls.Methods Two specimens each were obtained from the greater and lesser curvatures of the corpus and from the greater curvature of the antrum. The histopathological grading used was the updated Sydney System. Apoptotic epithelial cells were detected using the terminal deoxy nucleotidyl transferase-mediated deoxy-uridine triphosphate (dUTP) biotin nick-end labeling (TUNEL) method. The expression of Ki 67 was evaluated by immunostaining.Results Forty-five H. pylori-positive patients with endoscopic mucosal resection for early gastric cancer and 52 H. pylori-positive controls were studied. Gastric cancer was associated with a higher frequency of incomplete intestinal metaplasia (IM; odds ratio [OR], 19.1; 95% confidence interval [CI], 6.9–53.2; P < 0.001). The apoptotic index (AI) in the greater curvature of the corpus and the proliferation index (PI) in each part were significantly higher in cancer patients than in the control group. The median PI in the antrum was significantly higher in the incomplete IM group than that in the complete IM group (17.6 vs 12.6; P = 0.009). The PI and the AI in the greater curvature of the corpus correlated with the activity score, and the PI correlated with the IM score.Conclusions In the cancer patients, H. pylori-induced gastritis was associated with increased cell proliferation and apoptosis compared with mucosal findings in the controls. IM seems to be one of the most important factors affecting cell proliferation and may be one of the components of carcinogenesis that results in proliferation-dominant cell kinetics.     

Histological features of nodular gastritis and its endoscopic classification

OBJECTIVES: To clarify the histological features and endoscopic classifications of nodular gastritis (NG). METHODS: Overall 40 996 patients who had undergone an upper gastrointestinal endoscopy were enrolled. NG is defined as a uniform and diffuse protrusion from the antrum to angulus, which has two types at endoscopy: nodular (N) and granular (G). Three biopsy specimens were taken from the antrum, angulus and corpus. The histological features were evaluated using the updated Sydney System (USS). The topography of gastritis (antrum‐predominant, pangastritis or corpus‐predominant) and the prevalence of lymphoid follicles were also investigated. RESULTS: Overall 89 patients (0.22%) were diagnosed with NG, which tended to decrease in prevalence over age and predominantly affected women. All the patients were Helicobacter pylori‐positive. Among these, 65 patients underwent biopsy. Activity and inflammation were mostly moderate or severe, while intestinal metaplasia and atrophy were mostly absent at all three sites. Pangastritis was the most frequent (72%) type of gastritis. Lymphoid follicles were found in 69% at the antrum, 65% at the angulus and 51% at the corpus. There were no significant differences between N and G types in clinical features, USS scores, topography of gastritis, and prevalence of lymphoid follicles. CONCLUSIONS: Atrophy and intestinal metaplasia are rare but activity and chronic inflammation are severe at the antrum, angulus and corpus in NG. Pangastritis is the commonest type of gastritis. Lymphoid follicles affect everything up to the upper corpus, contrary to endoscopic protrusion found only at angulus. There was no correlation with pathological features between N and G types.