Proteomics analyses of Xiaopi granules in N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric epithelial dysplasia rat model using LC-MS.

Xiaopi granules have been shown to ameliorate gastric epithelial dysplasia in patients. However, the therapeutic mechanism is unclear. Herein, the proteomics method was applied to identify the differentially expressed proteins and related pathways. Sixty male Sprague-Dawley rats were randomly divided into four groups: control (C group, n = 10), model (M group), Xiaopi granules (X group), and vitacoenzyme (V group). The rat gastric epithelial dysplasia model was established by intragastrically administering N-methyl-N'-nitro-N-nitrosoguanidine and ranitidine and by orally administering 0.05% ammonia solution. After 12 weeks, the stomach tissue was analyzed by hematoxylin and eosin staining and proteomics analyses. Western-blot analysis was applied to further validate the proteomics results. Compared to the M group, levels of 326 and 350 proteins were altered significantly in the X and V groups (1.5-fold, p < 0.05), which were significantly enriched in digestion, metabolism, coagulation, and cell apoptosis. CELA2A, GHRL, NDUFB9, and PGC were significantly upregulated (p < 0.0001), whereas CLCA1, PLG, and DAC2 were downregulated (p < 0.001 or 0.0001) in the M group vs. the C group. The change in these proteins could be reversed after the treatment of Xiaopi granules or vitacoenzyme tablets. Xiaopi granules ameliorated gastric epithelial dysplasia by intervening in digestion, metabolism, blood coagulation, cell apoptosis, and other related pathways.

The pathology of gastric and duodenal polyps: current concepts.

The liberal use of upper endoscopy has led to an increased detection of gastric and duodenal polyps, which are identified in as many as 6 and 4.6% of patient examinations, respectively. Gastroduodenal polyps are a heterogeneous group of lesions that can be neoplastic or non-neoplastic (e.g. hyperplastic or heterotopical). Most polyps present characteristic topographical features, as well as endoscopic appearance and size. Evaluation of the surrounding mucosa is essential in assessing the underlying pathology (e.g. Helicobacter pylori, autoimmune gastritis or inherited polyposis syndromes). Phylogenetically, gastric and duodenal polyps can be classified according to the epithelial compartment from which they derive. Polyps that arise from the surface epithelium can either be of foveolar or intestinal type, and they can develop from either the native mucosa or the metaplastic epithelium (gastric intestinal metaplasia or duodenal foveolar metaplasia). Other polyps develop from the deeper glandular component, such as pyloric/oxyntic gland derived subtypes. In this review we focus upon epithelial polyps, with an emphasis on the most common and clinically relevant lesions, and present recently described entities.

Circulating microRNA-22-3p Predicts the Malignant Progression of Precancerous Gastric Lesions from Intestinal Metaplasia to Early Adenocarcinoma.

BACKGROUND: Gastric cancer has a poor outcome and identifying useful biomarkers from peripheral blood or tissue could allow its early detection, or potentially precancerous changes, thus improving the curative rates. MicroRNAs (miRNAs) have been shown to offer great potential in cancer diagnosis and prediction. AIM: Here, we investigated the role of plasma miRNAs in the natural course of gastric cancer, from intestinal metaplasia to early cancer. The findings were used to understand whether patients at a high risk of malignancy could be given appropriate interventions in the early disease process, such as using endoscopic submucosal dissection to treat gastric dysplasia or early gastric cancer. METHODS: Participants were divided into healthy control, intestinal metaplasia (IM), and dysplasia/early cancer (pT1a/b) groups. Microarray was used to select potential markers in tissue. RESULTS: Quantitative real-time polymerase chain reaction data showed circulating miRNA-22-3p had significantly different expression in patients with precancerous lesions or gastric adenocarcinoma. The areas under the curve of incomplete IM versus healthy control, low-grade/high-grade dysplasia, early gastric cancer, and GED were 0.8080, 0.8040, 0.8494, and 0.8095, respectively (all P values < 0.05). CONCLUSIONS: Circulating miRNA-22-3p could be a potential biomarker for gastric precancerous dysplasia and early cancer detection.

Gastric crypt dysplasia: a distinct subtype of gastric dysplasia with characteristic endoscopic features and immunophenotypic and biological anomalies.

AIMS: Previous reports have shown that gastric epithelial dysplasia (GED) limited to the crypt (gastric crypt dysplasia, GCD) is commonly identified at the periphery of gastric carcinoma. However, it is unknown whether GCD is endoscopically identifiable, and how it relates to classic GED lesions. METHODS AND RESULTS: We investigated 1196 consecutive endoscopic resections of GED lesions between January 2011 and December 2014. We also evaluated clinicopathological features of these lesions, as well as the immunohistochemical expression of mucin (Muc)2, Muc5AC, Muc6, CD10, Ki67 and p53. We found 51 (4.3%) lesions composed microscopically of GCD among 1196 GED lesions. Those were elevated mucosal lesions (66.7%) similar in colour and texture to the adjacent mucosa (68.6%). GCD was likely to have an antropyloric location and a higher grade than the adenomatous type, similar to the foveolar and hybrid types (P < 0.05). A gastric immunophenotype was more common in GCD compared to adenomatous GED (P < 0.05). Ki-67- and p53-positive cells were more evident in GCD compared to the adjacent gastric mucosa. CONCLUSIONS: Our results demonstrated that GCD can be an endoscopically identifiable lesion, sharing many similarities with foveolar and hybrid GED, for which it may represent a precursor lesion in the gastric carcinogenic sequence.

Occurrence of metachronous or synchronous lesions after endoscopic treatment of gastric epithelia dysplasia- impact of histologic features of background mucosa.

AIMS: Endoscopic resection is a safe and effective method to treat gastric epithelia dysplasia (GED). However, the development of metachronous and synchronous lesions after treatment has become a major concern. In this study, we investigated clinicopathologic features of 105 GED lesions from endoscopic resections between January 2008 and December 2009. Our goal is to find histologic factors that predict synchronous and metachronous lesions after ESD treatment. We assessed the degree of intestinal metaplasia (IM) and atrophy, type of IM, presence of gastritis cystica profunda, and crypt dysplasia in the adjacent mucosa. METHODS AND RESULTS: We divided 105 GED lesions into three groups: a single group without metachronous or synchronous GED or adenocarcinoma (n=35); a multiple synchronous group (n=30, group with synchronous occurrence of GED or adenocarcinoma after treatment); and a multiple metachronous group (n=40, group with metachronous occurrence of GED or adenocarcinoma after treatment). The multiple metachronous and synchronous groups showed larger sizes (p=0.003) and higher grades (p=0.021) as compared with the single group. Furthermore, marked IM and atrophy in adjacent mucosa were more easily seen in the multiple metachronous and synchronous groups as compared with the single group (p<0.0001). Interestingly, the presence of incomplete type of IM (p=0.025) and crypt dysplasia (p<0.0001) in background mucosa was associated with occurrence of metachronous and synchronous lesions following endoscopic resection of GED. CONCLUSIONS: The histological features of background mucosa, such as intestinal metaplasia, atrophy, and crypt dysplasia could be used as indicators of occurrence of metachronous and synchronous lesions after endoscopic treatment of GED.

Randomized double-blind clinical trial of Moluodan () for the treatment of chronic atrophic gastritis with dysplasia.

OBJECTIVE: To assess the efficacy and safety of Moluodan () in treating dysplasia in chronic atrophic gastritis (CAG) patients. METHODS: This was a multi-centered, double-blind, randomized controlled trial. The total of 196 subjects were assigned to receive either Moluodan or folic acid in a 2:1 ratio by blocked randomization. Mucosa marking targeting biopsy (MTB) was used to insure the accuracy and consistency between baseline and after 6-month treatment. Primary outcomes were histological score, response rate of pathological lesions and dysplasia disappearance rate. Secondary endpoints included gastroscopic findings, clinical symptom and patient reported outcome (PRO) instrument. RESULTS: Dysplasia score decreased in Moluodan group (P =0.002), significance was found between groups (P =0.045). Dysplasia disappearance rates were 24.6% and 15.2% in Moluodan and folic acid groups respectively, no significant differences were found (P =0.127). The response rate of atrophy and intestinal metaplasia were 34.6% and 23.0% in Moluodan group, 24.3% and 13.6% in folic acid group. Moluodan could improve erythema (P =0.044), and bile reflux (P =0.059), no significance between groups. Moluodan was better than folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite (P <0.05), with symptom disappearance rates of 37% to 83%. CONCLUSIONS: Moluodan improved dysplasia score in histopathology, and erythema and bile reflux score in endoscopy, and superior to folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite. [ChiCTR-TRC-00000169].

Differential LINE-1 Hypomethylation of Gastric Low-Grade Dysplasia from High Grade Dysplasia and Intramucosal Cancer.

BACKGROUND/AIMS: Gastric epithelial dysplasia is considered a precancerous lesion with a variable clinical course. There is disagreement, however, regarding histology-based diagnoses, which has led to confusion in choosing a therapeutic plan. New objective markers are needed to determine which lesions progress to true malignancy. We measured LINE-1 methylation levels, which have been reported to strongly correlate with the global methylation level in gastric epithelial dysplasia and intramucosal cancer. METHODS: A total of 145 tissue samples were analyzed by two histopathologists. All tissues were excised by therapeutic endoscopic mucosal resection and paired with adjacent normal tissue samples. A modified long interspersed nucleotide elements-combined bisulfite restriction analysis (COBRA-LINE-1) method was used. RESULTS: Gastric epithelial dysplasia and intramucosal cancer tissues had significantly lower levels of LINE-1 methylation than adjacent normal gastric tissues. High-grade dysplasia and intramucosal cancer were distinguishable from low-grade dysplasia based on LINE-1 methylation levels. Furthermore, the distinction could be determined with high sensitivity and specificity, as shown by the receiver operating characteristic (ROC) curve (AUC, 0.82; 95% confidence interval, 0.74 to 0.88). CONCLUSIONS: LINE-1 methylation levels may provide a diagnostic tool for identifying high-grade dysplasia and intramucosal cancer.

The diagnostic accuracy of endoscopic biopsy for gastric dysplasia.

PURPOSE: There is controversy over the treatment for low grade dysplasia, while resection is recommended for high grade dysplasia. But the concordance of the grade of dysplasia between pre- and post-resection is low because of sampling errors with endoscopic biopsy. We attempted to establish a clearer direction for the treatment of dysplasia by clarifying the discrepancy between the pre- and post-resection diagnoses. MATERIALS AND METHODS: We performed a retrospective review of 126 patients who had undergone resection with the diagnosis of dysplasia on biopsy at Bundang CHA Hospital from 1999 to 2009. RESULTS: Seventy patients were diagnosed with low grade dysplasia and 56 patients were diagnosed with high grade dysplasia. Among the 33 patients who received gastrectomy with lymph node dissection, 30 patients were revealed to have invasive cancers and 4 patients showed lymph node metastasis. Discordance between the diagnoses from biopsy and resection occurred in 55 patients (44%). There was no correlation on the comparative analysis between the size, location or gross type of lesion and the grade of dysplasia. CONCLUSIONS: The rate of discordance between the diagnoses of endoscopic biopsy and the post resection pathologic report was as high as 44%. Endoscopic mucosal resection was not sufficient for some patients who were diagnosed with dysplasia on biopsy due to the presence of lymph node metastasis. It is necessary to be prudent when determining the follow-up and treatment based solely on the result of the biopsy.