BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

Objective: To investigate the clinicopathological characteristics of esophageal carcinoma with gland duct differentiation. Methods: The clinical, morphologic and immunohistochemical (IHC) features of eight cases of esophageal carcinoma with gland duct differentiation diagnosed from 2012 to 2022 at the First Affiliated Hospital of Soochow University were summarized. Results: There were four males and four females, with a mean age of 68.5 (range 59-82) years. Two tumors were located in middle esophagus, five in the lower esophagus, and one in the cardia. The mean diameter was 2.4 cm (range 0.6-4.5 cm). The tumor had a bilayer epithelial structure, including the inner luminal epithelium and the outer basal epithelium. Immunohistochemistry showed that CK7 (8/8) and CK18 (8/8) were positive in the inner epithelium. p40 (8/8), p63 (8/8) and CK5/6 (8/8) were positive in the outer epithelium. SMA, calponin and CD117 were all negative. p53 mutants were found in all eight cases (strong and diffuse positivity in 6/8; complete loss of expression in 2/8). No columnar metaplasia, intestinal metaplasia and ectopic gastric mucosa were observed in the surface squamous epithelium in the cases. The mean follow-up time was 21.5 months (range 5-51 months). Seven patients survived and one patient died 31 months after surgery due to recurrence and liver metastasis. Conclusion: Esophageal carcinoma with esophageal gland duct differentiation is a rare tumor with unique histologic and IHC characteristics.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Esophageal Neoplasms/pathology* ; Epithelium/pathology* ; Metaplasia/metabolism* ; Carcinoma/pathology*

Objective To evaluate the gastric microbiome in patients with chronic superficial gastritis (CSG) and intestinal metaplasia (IM) and investigate the influence of Helicobacter pylori (H. pylori) on the gastric microbiome. Methods Gastric mucosa tissue samples were collected from 54 patients with CSG and IM, and the patients were classified into the following four groups based on the state of H. pylori infection and histology: H. pylori-negative CSG (n=24), H. pylori-positive CSG (n=14), H. pylori-negative IM (n=11), and H. pylori-positive IM (n=5). The gastric microbiome was analyzed by 16S rRNA gene sequencing. Results H. pylori strongly influenced the bacterial abundance and diversity regardless of CSG and IM. In H. pylori-positive subjects, the bacterial abundance and diversity were significantly lower than in H. pylori-negative subjects. The H. pylori-negative groups had similar bacterial composition and bacterial abundance. The H. pylori-positive groups also had similar bacterial composition but different bacterial relative abundance. The relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella were richer in the I-HP group than in G-HP group, especially Neisseria (t=175.1, P<0.001). Conclusions The gastric microbial abundance and diversity are lower in H. pylori- infected patients regardless of CSG and IM. Compared to H. pylori-positive CSG group and H. pylori-positive IM, the relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella is higher in H. pylori-positive patients with IM than in H. pylori-positive patients with CSG, especially Neisseria.
Gastric Mucosa/microbiology* ; Gastritis, Atrophic/microbiology* ; Gastrointestinal Microbiome/genetics* ; Helicobacter Infections/microbiology* ; Helicobacter pylori/genetics* ; Humans ; Metaplasia ; RNA, Ribosomal, 16S/genetics* ; Stomach Neoplasms

Objective: To study the clinicopathologic and genetic features of papillary cystic low-grade mucoepidermoid carcinoma (LG-MEC) and cystadenoma. Methods: A retrospective review was performed on salivary gland tumor patients with papillary cystic architecture who presented to department of oral pathology, Peking University School and Hospital of Stomatology between January 2010 and June 2022. Among this cohort, there were 17 males and 17 females with a range age of 23-82 years [(55.6±14.6) years]. Diagnosis was confirmed by histological, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis. Finally, 15 papillary cystic LG-MEC and 19 cystadenoma patients were included in the present study. All patients were followed clinically and radiologically, and the duration of follow-up ranged from 1 to 141 months. Results: All neoplasms showed papillary proliferation with multilocular or giant cystic tumors. Papillary cystic LG-MEC was characterized by epidermoid cells, intermediate cell and mucous cells with multiple lining-layers. Papillary cystic LG-MEC had mild cellular atypia and a pushing infiltration. Cystadenoma was characterized by cuboidal, columnar and ciliated pseudostratified columnar lining epithelium. Squamous metaplasia, mucinous metaplasia and acidophilic degeneration could also be observed focally in cystadenoma. For IHC staining, papillary cystic LG-MEC showed diffusely and strongly positive for mucin 4 (MUC4) (15/15) and mucin 5 Subtype AC (MUC5AC) (4/15) in the epidermoid cells, intermediate cell and mucous cells. The epidermoid cells and intermediate cells were diffusely positive for p40 and p63. The Ki-67 index was about 10%-15% in LG-MEC. As a contrast, p40 (17/19) and p63 (14/15) were only detected in the basal cells of cystadenoma. Cystadenoma showed focal MUC5AC (4/19)expression and MUC4 (19/19)diffuse expression. In addition, the Ki-67 index was 5%-10% in cystadenoma. The MAML2 gene translocation was detected in 11 LG-MEC patients, but none in cystadenoma. Conclusions: The differential diagnosis points between papillary cystic LG-MEC and cystadenoma included the specific epidermoid cells, intermediate cells and mucus cells in LG-MEC, cell atypia, the pushing-infiltration pattern, diffuse expression of p40 and p63 in the lining epithelium, and a MAML2 gene rearrangement. The molecular test of MAML2 should be recommended to reduce missed LG-MEC diagnoses.
Male ; Female ; Humans ; Carcinoma, Mucoepidermoid/pathology* ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/genetics* ; Biomarkers, Tumor/analysis* ; Salivary Gland Neoplasms/diagnosis* ; Transcription Factors/metabolism* ; Cystadenoma ; Metaplasia

Humans ; Melanoma ; Metaplasia ; Mucous Membrane ; Nasopharynx

Carcinogenesis ; Gastric Mucosa ; Helicobacter Infections ; Helicobacter pylori ; Humans ; Metaplasia ; Stomach ; Stomach Neoplasms

Endoscopic submucosal dissection is widely accepted as standard treatment for early gastric cancer; however, long-term management of metachronous gastric cancer after endoscopic resection is an important issue that is gaining much attention. Several prospective and retrospective studies have reported that Helicobacter pylori (H. pylori) eradication can reduce the risk of metachronous gastric cancer after endoscopic resection. Although there is lack of sufficient data regarding this subject, a few studies have reported histologically proven improvement in atrophic gastritis and intestinal metaplasia following H. pylori eradication in patients undergoing endoscopic resection. Therefore, treatment for H. pylori eradication should be considered in this patient population to reduce the incidence of metachronous gastric cancer and improve long-term outcomes.(
Gastritis, Atrophic ; Helicobacter pylori ; Helicobacter ; Humans ; Incidence ; Metaplasia ; Neoplasms, Glandular and Epithelial ; Neoplasms, Second Primary ; Prospective Studies ; Retrospective Studies ; Stomach Neoplasms

Helicobacter pylori (H. pylori) infection can cause gastric dysplasia and cancer via chronic inflammatory changes in the gastric mucosa that may lead to gastric atrophy and intestinal metaplasia. Many epidemiologic studies have demonstrated the prophylactic effects of H. pylori eradication on gastric cancer, and H. pylori eradication after endoscopic resection of early gastric cancer may prevent the occurrence of metachronous gastric cancer or dysplasia. Despite insufficient data on the effect of H. pylori eradication on gastric dysplasia and cancer before endoscopic resection, some studies have shown that H. pylori eradication can induce the regression or slow the progression of some gastric dysplasia. Therefore, eradication therapy before endoscopic resection may be effective in selected cases of low-grade dysplasia. However, endoscopic resection should be considered as the first-line treatment in high-grade dysplasia or early gastric cancer owing to the potential morphologic changes to some dysplasia or cancer that can be incurred by the eradication process, which may make it difficult to perform a subsequent endoscopic procedure.
Atrophy ; Epidemiologic Studies ; Gastric Mucosa ; Helicobacter pylori ; Helicobacter ; Metaplasia ; Stomach Neoplasms

BACKGROUND/AIMS: 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.METHODS: 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.RESULTS: 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).CONCLUSIONS: 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.
Atrophy ; Diagnosis ; Endoscopy ; Endoscopy, Gastrointestinal ; Follow-Up Studies ; Gastritis ; Gastritis, Atrophic ; Helicobacter pylori ; Humans ; Lymphoid Tissue ; Metaplasia ; Precancerous Conditions ; Stomach Neoplasms

OBJECTIVE: To assess the application of probe-based confocal laser endomicroscopy (pCLE) in diagnosis of gastric carcinoma and precancerous lesions. METHODS: Patients underwent pCLE in the First Affiliated Hospital of Zhejiang University School of Medicine during December 2013 and November 2014 and in the First Affiliated Hospital of Zhejiang Chinese Medical University during January 2014 and December 2017 were enrolled. The consistency between pCLE diagnosis and pathological diagnosis of gastric lesions, including atrophic gastritis, gastric intestinal metaplasia, low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia (including gastric carcinoma) was analyzed. RESULTS: Totally 154 gastric lesions from 119 patients were detected by pCLE. Using pathological diagnosis as gold standard, the sensitivity, specificity, coincidence rate and κ value of pCLE diagnosis for atrophic gastritis were 94.34%, 91.09%, 92.21%and 0.83; those indicators for gastric intestinal metaplasia were 84.47%, 92.16%, 87.01% and 0.72. The coincidence rate and κ value of pCLE diagnosis of complete gastric intestinal metaplasia were 0.75 and 0.49; for incomplete gastric intestinal metaplasia were 0.79 and 0.48, respectively. The sensitivity, specificity, coincidence rate and κ value of pCLE diagnosis for low-grade intraepithelial neoplasia were 85.29%, 87.50%, 87.01%and 0.66; those for high-grade intraepithelial neoplasia (including gastric carcinoma) were 95.83%, 97.17%, 96.75%and 0.92. CONCLUSIONS pCLE can be used for diagnosis of gastric carcinoma and pericancerous lesions and also for typing of gastric intestinal metaplasia.
Carcinoma ; diagnostic imaging ; Endoscopy, Gastrointestinal ; Humans ; Metaplasia ; Microscopy, Confocal ; Precancerous Conditions ; diagnostic imaging ; Sensitivity and Specificity ; Stomach ; diagnostic imaging ; pathology ; Stomach Neoplasms ; diagnostic imaging