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Background: Fusobacterium nucleatum inhabits the oral cavity and affects the progression of gastrointestinal cancer. Our prior findings link F. nucleatum to poor prognosis in oesophageal squamous cell carcinoma via NF-κB pathway. However, its role in oesophagogastric junction and gastric adenocarcinoma remains unexplored. We investigated whether F. nucleatum influences these cancers, highlighting its potential impact., Methods: Two cohorts of EGJ and gastric adenocarcinoma patients (438 from Japan, 380 from the USA) were studied. F. nucleatum presence was confirmed by qPCR, FISH, and staining. Patient overall survival (OS) was assessed based on F. nucleatum positivity. EGJ and gastric adenocarcinoma cell lines were exposed to F. nucleatum to study molecular and phenotypic effects, validated in xenograft mouse model., Results: In both cohorts, F. nucleatum-positive EGJ or gastric adenocarcinoma patients had notably shorter OS. F. nucleatum positivity decreased in more acidic tumour environments. Cancer cell lines with F. nucleatum showed enhanced proliferation and NF-κB activation. The xenograft model indicated increased tumour growth and NF-κB activation in F. nucleatum-treated cells. Interestingly, co-occurrence of F. nucleatum and Helicobacter pylori, a known risk factor, was rare., Conclusions: F. nucleatum can induce the NF-κB pathway in EGJ and gastric adenocarcinomas, leading to tumour progression and poor prognosis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Gastric atrophy caused by Helicobacter pylori infection was suggested to influence the risk of adenocarcinoma of the esophagogastric junction (AEGJ), however, the evidence remains limited. We aimed to examine the associations of H. pylori infection and gastric atrophy (defined using serum pepsinogen [PG] I to PGII ratio) with AEGJ risk, based on a population-based case-control study in Taixing, China (2010-2014), with 349 histopathologically confirmed AEGJ cases and 1859 controls. We explored the potential effect modification by H. pylori serostatus and sex on the association of serum PGs with AEGJ risk. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). H. pylori seropositivity was associated with an elevated AEGJ risk (OR = 1.95, 95% CI: 1.47-2.63). Neither CagA-positive nor VacA-positive strains dramatically changed this association. Gastric atrophy (PGI/PGII ratio ≤4) was positively associated with AEGJ risk (OR = 2.36, 95% CI: 1.72-3.22). The fully adjusted ORs for AEGJ progressively increased with the increasing levels of PGII (P-trend <.001). H. pylori showed nonsignificant effect modification (P-interaction = .385) on the association of gastric atrophy with AEGJ. In conclusion, H. pylori and gastric atrophy were positively associated with AEGJ risk. These results may contribute evidence to the ongoing research on gastric atrophy-related cancers and guide the prevention and control of AEGJ., (© 2021 UICC.)

Objective: To systematically evaluate the etiological association between esophagogastric junction adenocarcinoma and Helicobacter pylori (Hp) infection and the pathogenicity of Cag pathogenic island in Hp infection cases., Methods: Literatures about Hp infection and esophagogastric junction adenocarcinoma published from January 1980 to April 2015 were retrieved from CNKI, Wanfang data, VIP, the Cochrane Library, PubMed, EMBase databases. The literatures which met the inclusion criteria were collected and evaluated by using Newcastle-Ottawa Scale, then the heterogeneity was analyzed with Review Manager 5.3, and the pooled OR value and 95% confidence interval were calculated., Results: A total of 5547 study subjects were recruited in 13 studies, including 1446 esophagogastric junction adenocarcinoma cases and 4101 controls. The combined OR for Hp infection was 0.95 (95%CI: 0.66-1.36), P=0.71; The OR in high risk areas was 1.66 (95%CI: 1.33-2.08, P<0.001), higher than that in low-risk areas (0.68, 95%CI: 0.49-0.94, P=0.020). In addition, six studies found that the combined detection rates of Cag pathogenic island in esophagogastric junction adenocarcinoma cases and controls were 80.50% and 79.80%, respectively. There was no significant difference between two group, the combined OR was 1.24 (95%CI: 0.96-1.60)., Conclusion: The association between Hp infection and esophagogastric junction adenocarcinoma was not significant, however, the significant difference was observed between high risk area and low risk area; the detection rate of Gag pathogenic island in Hp infection cases was high, but the pathogenicity for esophagogastric junction adenocarcinoma needs further study.

In present work we studied the morphological features of the esophageal mucosa in 63 children with gastroesophageal reflux disease (GERD). The biopsies were taken at level of 3 cm above a Z-line and at level of 0.5-1 cm above a Z-line. The results of our study showed that the mucosa of the esophago-gastric junction may contain areas covered with columnar epithelium of 44.4% of children in the biopsies from the level of 0.5-1.0 cm above the Z-line. Inflammatory changes in the mucosa of the esophago-gastric junction identified in 71.4% of cases. The inflammation in the majority of cases (82.1%) was observed in the presence of H. pylori infection (p < 0.001). In addition, H. pylori in our study, we noted the relationship detection carditis in overweight child. When compared with the height-weight parameters, the excess body weight was observed in 17 of 28 patients. We couldn't found increasing detection of the cardia in patients with erosive GERD compared with non-erosive variants.

Background: The distal esophagus harbors a complex bacterial population. We hypothesized that a better understanding of bacterial communities in the esophagus would facilitate understanding of the role of bacteria in esophageal disease. Here, we investigated bacterial composition in the distal esophagus in subjects with a normal esophagus, reflux esophagitis, and Barrett's esophagus., Methods: Two biopsy specimens were obtained from the distal esophagus at 1 cm above the gastroesophageal junction under endoscopic examination in 18 patients (6 each with normal esophagus, reflux esophagitis, and Barrett's esophagus) and used for histological examination and DNA extraction. Fragments of 16S rDNA genes were amplified by PCR using general bacterial primers, and bacterial populations were examined. A third biopsy specimen was taken from the patients with Barrett's esophagus to histologically confirm the replacement of squamous epithelium with columnar epithelium in the distal esophagus., Results: Endoscopic diagnoses of normal esophagus, esophagitis, and Barrett's esophagus were confirmed by histological findings. The total amount of bacterial DNA detected did not significantly differ among groups (p > 0.1). On average, each of the 18 subjects yielded about 350 clones, of which 40 were randomly picked and sequenced. Analysis of 147 16S rDNA sequences from 240 clones of 6 subjects with normal esophagus yielded four phyla, Proteobacteria (49%), Firmicutes (40%), Bacteroidetes (8%), and Actinobacteria (3%). Similar analysis of 139 16S rDNA sequences from 240 clones of 6 patients with reflux esophagitis yielded 6 phyla, Proteobacteria (43%), Firmicutes (33%), Bacteroidetes (10%), Fusobacteria (10%), Actinobacteria (2%), and TM7 (2%). while that of 138 16S rDNA sequences from 240 clones of 6 cases of Barrett's esophagus yielded 5 phyla, Firmicutes (55%), Proteobacteria (20%), Bacteroidetes (14%), Fusobacteria (9%), and Actinobacteria (2%). Thus, microbial communities differed among patients with a normal esophagus, reflux esophagitis and Barrett's esophagus., Conclusions: Esophageal bacterial composition differs under conditions of normal esophagus, reflux esophagitis, and Barrett's esophagus. Diverse bacterial communities may be associated with esophageal disease.

Background and Aims: Barrett's esophageal cancer is usually included in gastroesophageal (GE) junction adenocarcinoma in Japanese people. No study on the pathogenesis of Barrett's esophageal cancer in comparison with GE junction adenocarcinoma other than Barrett's esophageal cancer has been reported in Japan. The aim of this study was to evaluate the clinical and pathological characteristics and gastric acid secretion of Barrett's esophageal cancer and GE junction adenocarcinoma other than Barrett's esophageal cancer in Japanese subjects., Material and Methods: Twenty-three patients with Barrett's esophageal cancer and 23 patients with GE junction adenocarcinoma other than Barrett's esophageal cancer were enrolled in this study. We evaluated and compared them by assessing the Helicobactor pylori (HP) infection status and gastric acid secretion using the endoscopic gastrin test (EGT)., Results: In the patients with Barrett's esophageal cancer, no significant difference was found in the mean EGT value between HP-positive and -negative patients, but in the patients with GE junction adenocarcinoma other than Barrett's esophageal cancer, the mean EGT value in HP-positive patients was significantly lower than that in HP-negative patients., Conclusion: Two distinct types of cancer of different origin may be mixed in GE junction adenocarcinomas. One is Barrett's esophageal cancer associated with high gastric acid secretion and reflux of gastric acid into the esophagus, the other is cancer resembling distal gastric cancer associated with gastric atrophy and low gastric acid secretion.

Endoscopical and histological features of oesophagogastroduodenal zone, parameters of pH-metry and electrogastroenterography, qualitative and quantitative characteristics of microbiocenosis were studied in 80 female persons with postcholecystectomy syndrome more then a year after cholecystectomy. In the presence of duodenogastral reflux the most natural is the combination of distal oesophagitis, antral atrophic gastritis and duodenitis, accompanied with low level of gastric acidity, gastric hypokinesis and duodenal dyskinesis, dysbacteriosis of mucosal microflora with its quantitative increase and appearance of bacteria with expressed pathogenicity non-typical for this biotope. These data should be taken into consideration for determination of pre- and postoperative treatment tactics for patients with gallstones.

Groups of gnotobiotic piglets were orally inoculated at 3 days of age with either Helicobacter heilmannii (Hh) or a newly described porcine-origin gastric Helicobacter pylori (Hp)-like bacterium. Three Hh-infected and 6 porcine Hp-like-infected swine were fed a milk replacement diet containing 5-10% (v/v) sterile corn syrup as a dietary source of fermentable carbohydrate. None of the piglets infected with Hh and supplemented with corn syrup developed gastric mucosal ulcers; 2 developed small erosive lesions in the pars esophagea. In contrast, all 6 dietary carbohydrate-supplemented Hp-like-infected swine developed severe gastroesophageal ulcers; 1 of these ex-sanguinated into the stomach and died before the end of the experiment. Four of these 6 piglets had grossly evident partially digested blood in the intestinal lumens, indicative of bleeding into the gastrointestinal tract from the stomach. These data suggest that a high carbohydrate diet and gastric colonization by porcine Hp-like bacteria facilitate development of clinically significant gastroesophageal ulcers.

The gastroesophageal junction (GEJ) is a poorly defined anatomic area that represents the junction etween the distal esophagus and the proximal stomach (cardia). The true anatomic GEJ corresponds to the most proximal aspect of the gastric folds, which represents an endoscopically apparent transition oint in most individuals. Many, if not most, adults, particularly those with either physiologic or logic GERD, have a proximally displaced Z-line indicating that the histologic squamocolumnar nction (SCJ) is located above the anatomic GEJ. The histologic characteristics of short segments of columnar mucosa located above the anatomic GEJ in these individuals are similar to the gastric cardia, ng composed of either pure mucous glands or mixed mucous glands/oxyntic glands. Although controversial, some authors believe that the cardia is normally composed, at birth, of surface mucinous columnar epithelium and underlying oxyntic glands identical to the gastric corpus, whereas others maintain that the true anatomic cardia is normally composed of mucinous columnar epithelium with underlying mucous glands or mixed mucous and oxyntic glands. However, the preponderance of evidence supports the latter theory and that the length of mucosa composed of either mucous, or mixed mucous glands/oxyntic glands, increases with age and is presumed to be related to ongoing GERD. Inflammation of the true gastric cardia (carditis), which is most often due to H. pylori infection, is difficult to distinguish from columnar metaplasia of the distal esophagus secondary to GERD. From a pathologist's perspective, the differential diagnosis of true gastric carditis from esophageal columnar metaplasia of the distal esophagus in GEJ biopsies is difficult, but a variety of clinical, pathologic, and immunohistochemical methods can be used to help separate these two disorders. Nearly one-third of patients who present for upper GI endoscopy without endoscopic evidence of BE reveal foci of intestinal metaplasia in the GEJ. There are some studies to suggest that the risk of dysplasia and cancer is different in patients with intestinal metaplasia in the cardia related to H. pylori infection versus those with metaplastic columnar epithelium in the distal esophagus related to GERD. Chronic inflammation is generally considered the predominant underlying stimulus for the development of columnar metaplasia in the GEJ, regardless of the etiology. Columnar metaplasia and intestinal metaplasia in the distal esophagus represents a squamous to columnar cell transition and there is some evidence that this occurs through an intermediate, or transitional, phase of intestinalization termed multilayered epithelium. In contrast, intestinal metaplasia that develops in the true gastric cardia secondary to H. pylori infection represents a columnar to columnar metaplastic reaction. This review will focus on the clinical, pathologic, and pathogenetic aspects of GERD and H. pylori-induced inflammation of the GEJ region.

Background and Aim: Helicobacter pylori-associated gastritis causes accumulation of reactive oxygen species in the mucosal compartment. This prospective study evaluates DNA oxidative damage in biopsy samples obtained from both the antrum and the gastroesophageal junction (GEJ) before and after H. pylori eradication., Patients and Methods: Thirty-two consecutive H. pylori-positive patients underwent endoscopy with multiple biopsy sampling (i.e., antrum, incisura angularis, fundus, and cardia at the GEJ). After H. pylori eradication, 32 patients underwent a checkup endoscopy (mean interval, 5.7 months); in a subgroup of 13 subjects, a third endoscopy procedure was also performed (mean interval, 18 months). Additional biopsy samples (two from the antrum and two from the GEJ) were used to assess 8-hydroxydeoxyguanosine (8OHdG) levels using both high-pressure liquid chromatography with electrochemical detector and ELISA., Results: In the antral compartment, no significant modifications of 8OHdG levels were assessed after H. pylori eradication. Conversely, following eradication, 8OHdG levels significantly increased (high-pressure liquid chromatography with electrochemical detector, P = 0.04; ELISA method, P = 0.05) in biopsy samples taken from the GEJ, and a further increase was documented in the subgroup of patients who underwent a third endoscopy (P = 0.01). The increasing trend was more relevant in patients in whom H. pylori-cagA-positive strains were eradicated and in those affected by hiatal hernia., Conclusions: The levels of DNA adducts in the antral mucosa are not modified by H. pylori eradication; conversely, H. pylori eradication significantly increases the oxidative adducts at the GEJ. The clinical and biological importance of this situation and whether and how it relates to a higher risk of precancerous lesions is open to debate.

At the gastric cardia, the molecular mechanisms of inflammation and metaplasia are incompletely understood. Thus, the aim of this study was to determine the expression of TFF1, TFF2 and TFF3 at this site and correlate these data with Helicobacter pylori infection or gastro-esophageal reflux disease (GERD). In 27 patients without intestinal metaplasia at the cardia, endoscopic biopsies were obtained for histology and RT-PCR. TFF1 and TFF2 were expressed in all cardia samples. TFF3 expression was significantly more frequent at the cardia (n = 15/24) than in the corpus (n = 2/26). TFF3 expression at the cardia was mainly observed in GERD patients, and there was a clear tendency towards higher interleukin-8 (IL-8) transcription levels; whereas TFF3 expression was not correlated with the H. pylori status or to tumor necrosis factor-alpha (TNF-alpha) expression. The expression of TFF3 at the cardia may represent an adaptation to GERD and precede the development of Barrett's esophagus.

For patients found to have intestinal metaplasia at the gastroesophageal junction, technical problems can make it difficult to distinguish short-segment Barrett's esophagus from intestinal metaplasia of the gastric cardia. Whereas the risk of malignancy for the former condition seems to be higher than that for the latter, the distinction between these conditions can have practical clinical implications. Immunostaining for cytokeratins has been proposed as a means to distinguish intestinal metaplasia of esophageal and gastric origins. We review recent data on this issue, and conclude that immunostaining for cytokeratins has no clear advantages over other biomarkers that have been proposed for identifying Barrett's esophagus (e.g., mucin histochemistry, mAb Das-1 immunoreactivity). Presently, the importance of intestinal metaplasia at the gastroesophageal junction remains unclear, and the clinical utility of biomarkers in distinguishing short-segment Barrett's esophagus from intestinal metaplasia of the gastric cardia has not yet been established.

Objective: Specialized intestinal metaplasia (SIM) is often found at a normal-looking gastroesophageal junction on routine biopsy. The prevalence of SIM in Asian populations has not been recorded. Its significance is also unclear. The objective of the study was to document the prevalence of SIM at the gastroesophageal junction in a Chinese population undergoing endoscopy., Methods: Biopsies were taken at the gastroesophageal junction in 145 patients, both at the squamocolumnar junction and immediately below in the gastric cardia. Specimens were examined for the type of epithelium (squamous, cardiac, and fundic), the presence of SIM, and Helicobacter pylori (H. pylori)., Results: Of 145 patients who underwent endoscopy, 136 had a normal-looking gastroesophageal junction. Cardiac epithelium was found in 100 patients. Of these 100 patients, SIM was documented in 34% of patients and carditis in 20%. Patients with SIM were older compared with those without SIM (mean age 62 yr and 56 yr, p = 0.035). Carditis was more prevalent in patients with SIM. It was present in 11 out of 34 patients who had SIM (32.4%) compared with nine in 66 patients (13.6%) without SIM, p = 0.036. When carditis was found, H. pylori was present at the cardia in 40% of patients (eight of 20) compared with only 18% (14 of 80) in those without carditis, p = 0.039., Conclusions: SIM is prevalent at the gastroesophageal junction in Chinese patients undergoing endoscopy and is associated with carditis. Carditis in turn may be related to H. pylori infection.

Background: The role of Helicobacter pylori infection and/or gastro-oesophageal reflux disease in pathogenesis of intestinal metaplasia in gastric cardia is still unclear., Aims: To prospectively evaluate prevalence of inflammation and intestinal metaplasia of cardia in relationship to Helicobacter pylori infection in patients with gastro-oesophageal reflux disease and in healthy controls., Patients: A total of 122 consecutive patients with gastro-oesophageal reflux disease and 49 control subjects were included., Methods: During endoscopy, a total of six biopsies were taken from antrum, corpus and cardia. Helicobacter pylori infection was assessed by histology and rapid urease test. Degree of chronic gastritis, inflammatory activity and Helicobacter pylori colonization were scored from 0 to 3., Results: No difference in prevalence was observed between gastro-oesophageal reflux disease patients and controls as far as concerns Helicobacter pylori (41% vs 38%), inflammation of cardia (59.5% vs 70%) and intestinal metaplasia of cardia (18% vs 19%). Inflammation of cardia was significantly (p<0.001) associated with Helicobacter pylori irrespective of gastro-oesophageal reflux disease symptoms. Cardial intestinal metaplasia was more frequently (p=0.03) found in infected subjects ((27%) than in uncolonized subjects (13%). No relationship was observed between gastro-oesophageal reflux disease and carditis and cardial intestinal metaplasia. Cardial intestinal metaplasia was more frequently detected in association with carditis (26% vs 6%, p=0.001)., Conclusions: Inflammation and intestinal metaplasia of the gastric cardia are not markers of gastro-oesophageal reflux disease but are related to Helicobacter pylori.

Objective: Endoscopy with biopsy is an important diagnostic procedure in patients with gastro-oesophageal reflux disease. However, it is still unclear whether histological findings such as intestinal metaplasia, squamous epithelial hyperplasia, and carditis should have an impact on patient management, and whether routine biopsies at the gastro-oesophageal junction should be taken., Design: Patients undergoing routine gastroscopy for various indications were biopsied twice just below, directly at, and right above the gastro-oesophageal junction., Methods: Clinical symptoms, endoscopic oesophagitis, and histopathologies such as carditis, reflux disease, and intestinal metaplasia were determined and graded., Results: Epithelial hyperplasia suggestive of reflux disease (63%), chronic carditis (94%), active carditis (40%), foveolar hyperplasia (75%), and intestinal metaplasia (14%) were frequently observed. For patients with a normal appearing Z-line, there was a weak correlation of intestinal metaplasia at the cardia with intestinal metaplasia in the stomach (Spearman's R = 0.2, P = 0.008), but no correlation with either chronic or active carditis, or with epithelial hyperplasia in the oesophagus. There was no correlation between H. pylori status or symptoms of reflux disease with epithelial hyperplasia. The severity of chronic and active carditis was closely correlated with H. pylori status (R = 0.37, P < 0.00001). The median time for gastroscopy in 30 control patients was 4.6 min, while endoscopy with additional biopsies at the gastro-oesophageal junction took a median of 8 min (U-test, P < 0.00001)., Conclusions: Intestinal metaplasia at the gastro-oesophageal junction was encountered too frequently to warrant regular follow-up in a surveillance programme. Correlation of epithelial hyperplasia with symptoms of reflux disease is poor. We propose that routine biopsy at the gastro-oesophageal junction is not warranted until an impact on patient management can be demonstrated.

Objective: The clinical significance of chronic inflammation at the gastroesophageal junction (carditis) is unknown: it may be associated with Helicobacter pylori (H. pylori) gastritis or with gastroesophageal reflux disease (GERD). We aimed to examine the association between carditis and H. pylori gastritis and endoscopic erosive esophagitis., Methods: One thousand and fifty-three patients undergoing gastroscopy were enrolled in the study. Biopsy specimens were obtained from gastric antrum and corpus, immediately distal to normal-appearing squamocolumnar junction and distal esophagus., Results: Chronic inflammation at the gastroesophageal junctional mucosa (carditis) was detected in 790 (75%) of 1053 patients. The male:female ratio of the carditis group was 1:1.5 and of the noncarditis group 1:1.6 (p = 0.6). The mean age of the carditis group was 58.7 yr (95% confidence interval [CI], 57.6-59.9) and of the noncarditis group, 52.6 yr (95% CI, 50.7-54.6, p < 0.001). Of the carditis group (N = 790), 549 (69%) had chronic gastritis (70% H. pylori positive) and 241 (31%) had normal gastric histology. In multivariate analyses, the only risk factor for carditis in subjects with chronic gastritis was H. pylori infection (odds ratio [OR], 2.9; 95% CI, 1.6-5.0), whereas the independent risk factor for carditis in subjects with histologically normal stomach was endoscopic erosive esophagitis (OR, 1.8; 95% CI, 1.1-3.1). The prevalence of complete intestinal metaplasia (IM) in the gastric cardia mucosa was 7% in the noncarditis group, 19% (p < 0.001) in the carditis group with chronic gastritis, and 10% (p = 0.3) in the carditis group with normal stomach. The respective prevalences of incomplete IM were 3%, 12% (p < 0.001), and 12% (p < 0.001). Among carditis patients with normal stomach histologically (N = 241), those with complete and/or incomplete IM (N = 49) were older than those with carditis only (63.6 yr [95% CI, 59.9-67.2] vs 51.4 yr [95% CI, 48.9-53.9]; p < 0.001)., Conclusions: Two dissimilar types of chronic inflammation of the gastric cardia mucosa seem to occur, one existing in conjunction with chronic H. pylori gastritis and the other with normal stomach and erosive GERD. Most cases of chronic gastric cardia inflammation and intestinal metaplasia are detected in patients with chronic H. pylori gastritis.

Erosions and gastroesophageal ulcers (GEU) were produced in the pars esophagea of young gnotobiotic swine fed a carbohydrate-enriched liquid diet and monoinfected with two different fermentative commensal bacteria, Lactobacillus and Bacillus sp. In contrast, piglets, fed a similar diet and inoculated with Gastrospirillum sp. (Helicobacter heilmannii), a helicobacter species that colonizes the gastric mucosa, did not develop GEU. Experimental GEU likely develops secondary to epithelial damage mediated by microbial-origin acids whose production is potentiated by high dietary carbohydrate and parietal cell-origin hydrochloric acid.