Randomized double-blind clinical trial of Moluodan () for the treatment of chronic atrophic gastritis with dysplasia / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of Moluodan () in treating dysplasia in chronic atrophic gastritis (CAG) patients.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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%.</p><p><b>CONCLUSIONS</b>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].</p>

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.

Treatment of Gastric Epithelial Dysplasia That Is Diagnosed by Endoscopic Biopsy

PURPOSE: Gastric epithelial dysplasia (GED) was defined as "unequivocally neoplastic epithelium that may be associated with or give rise to invasive adenocarcinoma" and GED also represents a direct precursor of intestinal type adenocarcinoma of the stomach. The recommended treatment guidelines for GED in the medical literature are endoscopic mucosal resection (EMR) or surgery for high grade dysplasia (HGD) and annual endoscopic surveillance with biopsy for low grade dysplasia (LGD) The aim of this study was to determine the treatment plan for GED that is diagnosed by endoscopic biopsy. MATERIALS AND METHODS: We enrolled 148 patients who were treated by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for GED: there were 63 patients with HGD and 85 patients with LGD and all of them were diagnosed by endoscopic biopsy from January 2006 to December 2008. The results of the final histopathologic reports after EMR or ESD were compared with the results of the endoscopic biopsies. RESULTS: The final histopathologic results of the 148 patients with GED showed 49 (33.1%) patients with adenocarcinoma, 40 (27.0%) patients with HGD and 59 (39.9%) patients with LGD. Among the 63 patients with HGD, 34 (54.0%) patients had adenocarcinoma, 20 (31.7%) patients had HGD and 9 (14.3%) patients had LGD. For the 85 patients with LGD, 15 (17.6%) patients had adenocarcinoma, 20 (23.5%) patients had HGD and 50 (58.8%) patients had LGD. CONCLUSION: Complete resection, including EMR or ESD, is needed for patients with GED diagnosed by endoscopic biopsy and they have HGD. For patients with LGD, EMR or ESD may be needed in addition to endoscopic surveillance with biopsy for making the correct diagnosis and proper treatment because of the possibility of adenocarcinoma.

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.

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.

Therapeutic Strategy and Clinicopathologic Analysis of Gastric Epithelial Dysplasia

PURPOSE: Although the role of gastric epithelial dysplasia (GED) as a biological and morphological precursor of gastric cancer has been widely investigated, controversy remains with regard to the pathological grading systems and therapeutic strategies. The purpose of this retrospective study was to analysis the clinicopathological characteristics and treatment results of GED and to establish a rational therapeutic strategy for its use. METHODS: Between 1999 and 2002, a review and analysis of 72 patients initially diagnosed as GED was undertaken. RESULTS: 38.4% of low grade dysplasia (LGD) progress to high grade dysplasia (HGD), and 25% of the progressed HGD are diagnosed as an adenocarcinoma by definitive treatment. 40% of HGD cases progress to adenocarcinoma. In 10 of 54 cases a repeated endoscopic examination revealed an adenocarcinoma. 2 of 10 cases were diagnosed as LGD on the first endoscopic examination. However, these cases had a definitive operation after being diagnosed as HGD on a follow up endoscopic biopsy. 8 of 10 cases were diagnosed as HGD on the first endoscopic examination. There were 10 adenocarcinoma cases were no lymph node metastasis. 9 cases had invasion of the mucosal layer and 1 of the muscularis layer. CONCLUSION: Cases diagnosed as LGD require persistent and repeated endoscopic examinations. Cases diagnosed as HGD require frequent and multifocal endoscopic biopsies to detect coexisting or transient carcinomas. The therapeutic strategy for HGD might be EMR, endoscopic assisted operation or a gastrectomy, depending on the patient's general condition and the size and location of the dysplastic lesion.

Study of the Expression of FasL and of Apoptosis in Gastric Epithelial Dysplasia and Gastric Adenocarcinomas

PURPOSE: This study was to observe whether the apoptotic function of tumor-infiltrating lymphocytes (TIL) is induced in human gastric epithelial dysplasia and gastric adenocarcinoma according to the role of FasL expression. MATENRIALS AND METHODS: A total of 56 gastric epithelial dysplasia and gastric adenocarcinoma patients were enrolled in this study: 9 cases of gastric epithelial dysplasia, 18 cases of early gastric carcinomas (EGC) and 29 cases of advanced gastric carcinomas (AGC). Immunohistochemical staining was performed for FasL and CD45, and the terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) method was used to detect cell death in tumor-infiltrating lymphocytes. RESULTS: 1) Positive reactions of FasL to neoplastic cells were 88.9% (8/9) in gastric epithelial dysplasia, 83.3% (15/18) in EGC, and 75.9% (22/29) in AGC. 2) Expression of TIL was decreased in the FasL positive region and was increased in the FasL negative region, and significant expression of TIL was observed in the AGC group (P=0.001). 3) Expression of apoptotic TIL was very similar to the FasL expression, and 100% expression was observed in gastric epithelial dysplasia group. 4) Expression of apoptotic TIL was increased in the FasL positive region and decreased in the FasL negative region, and significant apoptotic expression was observed in the gastric epithelial dysplasia and EGC groups (P=0.0420, P=0.0263, respectively). CONCLUSION: These results suggest that FasL is a prevalent mediator of immune privilege in epithelial dysplasia and cancer of the stomach.

Expression of p53,Cdk_4 and Survivin in gastric epithelial dysplasia with colonic and small intestinal metaplasia / 中国医师杂志

Objective To evaluate the significance of p53,Cdk_4 and Survivin in gastric epithelial dysplasia with colonic and small intestinal metaplasia.Methods Immunohistochemical SP method was used to detect p53,Cdk_4,and Survivin in 44 cases of colonic intestinal metaplasia(27 low grade epithelial dysplasia,17 high grade epithelial dysplasia) and 51 cases of small intestinal metaplasia(42 low grade epithelial dysplasia,9 high grade epithelial dysplasia) by endoscope.Results The positive expression rates of p53 and Survivin had significant difference in two types of intestinal metaplasia and the difference was significant between low-grade and high-grade epithelial dysplasia.The expression of CDK_4 had significant difference in two types of intestinal metaplasia and had not difference between low-grade and high-grade epithelial dysplasia.Conclusion The expressions of p53,CdK_4 and Survivin are closely associated not only with the types of intestinal metaplasia but also with the different grades of epithelial dysplasia.The expression of p53,Cdk_4,and Survivin may be valuable markers in assessing the biological behavior of gastric epithelial dysplasia with intestinal metaplasia.