Determination of an Appropriate Endoscopic Monitoring Interval for Patients with Gastric Precancerous Conditions in China

Objective Gastric precancerous conditions such as atrophic gastritis(AG)and intestinal metaplasia(IM)are considered independent risk factors for gastric cancer(GC).The suitable endoscopic monitoring interval is unclear when we attempt to prevent GC development.This study investigated the appropriate monitoring interval for AG/IM patients.Methods Totally,957 AG/IM patients who satisfied the criteria for evaluation between 2010 and 2020 were included in the study.Univariate and multivariate analyses were used to determine the risk factors for progression to high-grade intraepithelial neoplasia(HGIN)/GC in AG/IM patients,and to determine an appropriate endoscopic monitoring scheme.Results During follow-up,28 AG/IM patients developed gastric neoplasia lesions including gastric low-grade intraepithelial neoplasia(LGIN)(0.7%),HGIN(0.9%),and GC(1.3%).Multivariate analysis identified H.pylori infection(P=0.022)and extensive AG/IM lesions(P=0.002)as risk factors for HGIN/GC progression(P=0.025).Conclusion In our study,HGIN/GC was present in 2.2%of AG/IM patients.In AG/IM patients with extensive lesions,a 1–2-year surveillance interval is recommended for early detection of HIGN/GC in AG/IM patients with extensive lesions.

Gastric epithelial histology and precancerous conditions

The most common histological type of gastric cancer(GC)is gastric adenocarcinoma arising from the gastric epithelium.Less common variants include mesenchymal,lymphoproliferative and neuroendocrine neoplasms.The Lauren scheme classifies GC into intestinal type,diffuse type and mixed type.The WHO classification includes papillary,tubular,mucinous,poorly cohesive and mixed GC.Chronic atrophic gastritis(CAG)and intestinal metaplasia are recommended as common precancerous conditions.No definite precancerous condition of diffuse/poorly/undifferentiated type is recommended.Chronic superficial inflammation and hyperplasia of foveolar cells may be the focus.Presently,the management of early GC and precancerous conditions mainly relies on endoscopy including diagnosis,treatment and surveillance.Management of precancerous conditions promotes the early detection and treatment of early GC,and even prevent the occurrence of GC.In the review,precancerous conditions including CAG,metaplasia,foveolar hyperplasia and gastric hyperplastic polyps derived from the gastric epithelium have been concluded,based on the overview of gastric epithelial histological organization and its renewal.

Tumor suppressor gene p16 and Rb expression in gastric cardia precancerouslesions from subjects at a high incidence area in northern China

AIM:To further understand the molecular basis for gastric cardia carcinogenesis and to provide etiological clues. METHODS: Endoscopic mucosa biopsy and histopathological examinations were made on 37 subjects from a high incidence area for both esophageal and gastric cardia carcinomas in northern China. All the biopsy samples were fixed in 850 ml. (-1)L alcohol and embedded in paraffin. Each block contained one piece of tissue and was serially section at 5 microm. Immunohistochemistry (ABC) was carried out on these gastric cardia samples to determine the alterations of p16 and Rb. RESULTS: Based on the histopathlogical examination there were 11 cases of chronic superficial gastritis, 12 cases of chronic atrophic gastritis and 14 cases of dysplasia. The immunostaining demonstrated different levels of unclear immunostaining of p16 and Rb in normal gastric cardia tissue and the tissues with different severity of lesions. With the lesions progressing, the positive immunostaining rates for p16 protein had a decreasing tendency. In contrast, the positive immunostaining rate for Rb protein had an increasing tendency. There was a significant negative relationship between the two parameters. Changes of p16 was CSG 11(100%), CAG 7(58%), DYS 4(29%) and changes of Rb was CSG 2(18%), CAG 8(67%) and DYS 12(86%), (P【0.05). CONCLUSION: The alterations of p16 and Rb protein may play a role in the early stages of gastric cardia carcinogenesis.

Possibility of non-invasive diagnosis of gastric mucosal precancerous changes

AIM: To assess the possibility of non-invasive screening of atrophic chronic gastritis for preventing further development of gastric cancer.METHODS: One hundred and seventy-eight consecutive Helicobacter pylori ( H pylori)-positive dyspeptic patients after detection of serum levels of pepsinogen-1 (PG-1) and gastrin-17 (G-17) by enzyme immunoassay were proposed for endoscopy and histology. The serologic and morphologic results were compared with estimating the sensitivity, specificity and prognostic values of the tests.RESULTS: There was statistically significant reverse dependence between the grade of stomach mucosal antral or corpus atrophy and the proper decreasing of serum G17 or PG1 levels. The serologic method was quite sensitive in the diagnosis of non-atrophic and severe antral and corpus gastritis. Also, it was characterized by the high positive and negative prognostic values.CONCLUSION: Detection of serum G-17 and PG1 levels can be offered as the screening tool for atrophic gastritis. The positive serologic results require further chromoendoscopy with mucosal biopsy, for revealing probable progressing of atrophic process with development of intestinal metaplasia, dysplasia or gastric cancer.

Effects of San Qi on Gastric Secretion and Protective Factors of Gastric Mucosa in the Rat with Precancerous Lesion of Stomach

In the model rat with precancerous lesion of stomach induced by the combined method of insertion of a spring into the pylorus and high salt hot paste,effects of San Qi (三七 Radix Notoginseng) on gastric secretion and protective factors of stomach were investigated.The results indicated that gastric secretion,gastric mucosal blood flow (GMBF) and aminohexose content lowered significantly,and malondialdehyde (MDA) increased significantly (P<0.01) in the model group as compared with the normal group;after treatment with San Qi Powder for 12 weeks,both gastric secresion and GMBF increased,and MDA content decreased as compared with the negative control group (P<0.01),with no significant increase of aminohexose content.It is suggested that San Qi (三七 Radix Notoginseng) may improve gastric secretion,and that increase of GMBF and antagonism against the lesion of oxygen free radicals are possibly one of its mechanisms.

Expression of bcl-2 oncogene in gastric precancerous lesions and its correlation with syndromes in traditional Chinese medicine

AIM: To observe the protein and mRNA expression of bcl-2 oncogene in gastric precancerous lesions (GPL) and to analyze its correlation with syndromes in traditional Chinese medicine (TCM). METHODS: Sixty-seven patients with GPL confirmed by gastroscopy and pathology were studied,including 39 cases of moderate gastric mucosal dysplasia,19 cases of severe gastric mucosa dysplasia, 9 cases of incomplete colon metaplasia. In syndrome differentiation of TCM,17 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by qi stagnation, 21 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by stomach heat, 29 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by blood stasis. Protein and mRNA expression of bcl-2 oncogene were detected by labeled streptavidin biotin (LSAB) immunohist-ochemistry and in situ hybridization respectively. RESULTS: Abnormal expression of protein and mRNA on bcl-2 oncogene was found in GPL,which increased gradually with the course of lesions. In moderate and severe gastric mucosal dysplasia and incomplete colon metaplasia,there was no difference in the expression of bcl-2 oncogene (P>0.05).In different accompanying syndromes, the expression of protein and mRNA on bcl-2 oncogene increased gradually in the following order: deficiency of both qi and yin of the spleen and stomach accompanying qi stagnation→stomach heat→blood stasis. In GPL, compared with accompanying blood stasis, there was an obvious difference in the expression of bcl-2 oncogene between the syndrome of qi and yin deficiency of the spleen and stomach and accompanying stomach heat, so did accompanying qi stagnation (the level of protein: X2=8.45, P<0.05;the level of mRNA: X2=7.35, P<0.05). CONCLUSION: Apoptosis-associated bcl-2 oncogene is abnormally expressed in GPL,which correlates with different accompanying syndromes in TCM.

Function of apoptosis and expression of the proteins Bcl-2,p53 and C-myc in the development of gastric cancer

INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .

Endoscopic features predictive of gastric cancer in superficial lesions with biopsy-proven high grade intraepithelial neoplasia

AIM:To investigate the macroscopic and clinicopathologic features of gastric cancer in patients with biopsy-suggested high grade intraepithelial neoplasia. METHODS:Patients with biopsy-confirmed gastric high grade intraepithelial neoplasia were reviewed from January 2001 to March 2008.Pathologic sections were re-evaluated by two senior pathologists. Patients with an en-bloc resection of the lesion within two months after the diagnosis of high grade intraepithelial neoplasia were enrolled in the study. Clinical manifestations,endoscopic features,biopsy and surgical pathology of all patients were collected and analyzed.The data acquired were subjected to univariate and multivariate analysis. RESULTS:Seventy-two superficial gastric lesions with a pathologic diagnosis of high grade intraepithelial neoplasia based on biopsy specimens were enrolled. True high grade intraepithelial neoplasia was finally proved in 16 lesions and gastric cancer in the rest 56 lesions,most of which(96.4%)were differentiated carcinomas.The result of univariate analysis indicatedthat the size and the presence of marked ulcer plaque or scar in a superficial lesion were independently associated with gastric cancer(P<0.05),when high grade intraepithelial neoplasia was diagnosed by biopsy pathology.The results of multivariate analysis revealed the size greater than 1.5 cm[odds ratio(OR)18.400,P<0.001]and the presence of 5-odd mm ulcer plaque or scar(OR 10.000,P=0.044)were associated with gastric cancer.Accordingly,the sensitivity,specificity and negative predictive value of multivariate analysis for predicting"true high grade intraepithelial neoplasia" was 87.5%,89.3%and 96.2%,respectively. CONCLUSION:Macroscopic findings are of value in differentiation between high grade intraepithelial neoplasia and superficial gastric cancer.This may simplify patient work-up and save costs for patients and healthcare system.

Confocal laser endomicroscopy in the “in vivo” histological diagnosis of the gastrointestinal tract

Recent technological advances in miniaturization have allowed for a confocal scanning microscope to be integrated into a conventional flexible endoscope,or into trans-endoscopic probes,a technique now known as confocal endomicroscopy or confocal laser endomicroscopy.This newly-developed technology has enabled endoscopists to collect real-time in vivo histological images or "virtual biopsies" of the gastrointestinal mucosa during endoscopy,and has stimulated significant interest in the application of this technique in clinical gastroenterology.This review aims to evaluate the current data on the technical aspects and the utility of this new technology in clinical gastroenterology and its potential impact in the future,particularly in the screening or surveillance of gastrointestinal neoplasia.

Advances in the Researches on the Blocking Effect of Chinese Drugs on Tumors

Malignant tumors are caused by multiple carcinogenic factors undergoing several stages. The occurrence and development of tumors may be prevented and blocked if some effective interference factors are brought into play.1 At present, there are two main subjects for the researches, that is, blocking the precancerous lesions and blocking the develop-ment of tumors. The former focuses on the removing of carcinogenic factors and on the chemoprophylaxis of cancer, while the latter on the inhibition of cancer cell infiltration and cancerometastasis. These are summarized as follows.

A STUDY ON CYCLOOXYGENASE -2 PROTEIN EXPRESSION IN ESOPHAGEAL CAICONOGENESIS

Objective: To investigate cyclooxygenase- 2(Cox-2) protein expression in esophageal cancer and precancerous lesions. Methods: One hundred twenty biopsy specimens from esophageal carcinoma and 113 from patients with esophageal premalingnant lesions, 27 from individuals with normal esophageal mucosa and 3 from Barrett’s esophagus were examined for Cox-2 protein expression by immunohistochemistry. Results: Cox-2 protein was not observed in normal esophageal squamous and glandular epithelium, hyperplasia from mild to severe dysplasia lesions and carcinoma in situ. Positive Cox-2 protein expression was found in 4 of 60 specimens of invasive squamous-cell carcinomas, 21 of 30 specimens of esophageal adenocarcinomas and in 3 of 3 Barret’s esophageal tissues. Conclusion: The Cox-2 protein expression may be associated with the development of the esophageal adenocarcinomas but not esophageal squamous-cell carcinomas.

Expression of glutathione S-transferase placental mRNA in hepatic preneoplastic lesions in rats

IM To detect glutathione Stransferase placental (GSTP) mRNA expression in hepatic preneoplastic lesions in rats.METHODS Using SolitFarber model, the GSTP mRNA expression was observed in hepatic preneoplastic lesions induced by diethylnitrosamine (DEN) in rats and normal and regenerated hepatic tissues in the control group by in situ hybridization.RESULTS GSTP mRNA was mainly expressed in altered hepatic foci (AHF) and some of the oval cells in hepatic preneoplastic lesions and the extent of its expression was different among various foci or/and positive cells in the same focus whereas no expression was observed in normal and regenerated hepatic tissues.CONCLUSION Cells in AHF and oval cells may be the preneoplastic cells in the experimental hepatocellular carcinoma at the molecular level and heterogeneity exists in GSTP transcription levels..

Expression of telomerase genes in cancer development in atypical hyperplasia of the mammary duct

OBJECTIVE: To investigate telomerase gene expression in precancerous mammary lesion, such as atypical ductal hyperplasia and breast cancer and to study the relationship between expression and malignant transformation. METHODS: Expression of human telomerase genes (hTR) and human reverse transcriptase gene (hTRT) in 76 cases of mammary tissue was evaluated using in situ hybridization and included 50 cases of mammary hyperplasia, 6 of which were benign hyperplasia, 9 were mild atypical hyperplasia, 12 were moderate atypical hyperplasia, 23 were severe atypical hyperplasia and 26 were mammary cancer. RESULTS: The expressions of hTR and hTRT mRNA were much weaker or negative in benign hyperplasia (16.6%, 0), weak to mild moderate in atypical hyperplasia (22.2%, 11.1%, 33.3%, 25.0%), strong in severe atypical hyperplasia (60.9%, 52.1%), and significantly strong in mammary cancer (88.5%, 80.8%).The difference between mild-moderate atypical hyperplasia, invasive ductal carcinoma and severe atypical hyperplasia was significant (P 0.05). CONCLUSION: Telomerase genes (hTR and hTRT) expressions are related to the transformation of atypical hyperplasia. Activated telomerase may play a role in mammary cancer development.

Telomerase activity analysis of esophageal carcinoma using microdissection-TRAP assay

OBJECTIVES: To investigate telomerase activity in esophageal squamous cell carcinoma (SCC) and its preneoplasia lesions, and to study the relationships between telomerase activity and cancer differentiation, cancer invasiveness, and lymphatic metastasis. METHODS: Telomerase activity in esophageal SCC tissues, adjacent dysplasia tissues and normal epithelia from the surgical edge were assessed by microdissection-TRAP (telomeric repeat amplification protocol)-silver staining assay. RESULTS: Telomerase activity was detected in 37 (82.2%) of 45 esophageal tumors, 23 (79.3%) of 29 dysplasias, and 2 (5%) of 40 normal epithelia. There was a significant difference in activity between dysplasia and normal epithelium, as well as between tumor and normal epithelium. Twenty-six (92.9%) of 28 tumors with lymphatic metastasis had detectable telomerase activity compared to 11 (64.7%) of 17 non-lymphatic metastasis tumors. These relationships were statistically significant (P