AIM: To investigate the indication, feasibility, safety, and clinical utility of endoscopic submucosal dissection (ESD) in the management of various gastrointestinal pathologies. METHODS: The medical records of 60 con...AIM: To investigate the indication, feasibility, safety, and clinical utility of endoscopic submucosal dissection (ESD) in the management of various gastrointestinal pathologies. METHODS: The medical records of 60 consecutive patients (34 female, 26 male) who underwent ESD at the gastroenterology department of Kocaeli University from 2006-2010 were examined. Patients selected for ESDhad premalignant lesions or non-invasive early cancers of the gastrointestinal tract and had endoscopic and histological diagnoses. Early cancers were considered to be confined to the submucosa, with no lymph node involvement by means of computed tomography and endosonography. RESULTS: Sixty ESD procedures were performed. The indications were epithelial lesions (n = 39) (33/39 adenoma with high grade dysplasia, 6/39 adenoma with low grade dysplasia), neuroendocrine tumor (n = 7), cancer (n = 7) (5/7 early colorectal cancer, 2/7 early gastric cancer), granular cell tumor (n = 3), gastrointestinal stromal tumor (n = 2), and leiomyoma (n = 2). En bloc and piecemeal resection rates were 91.6% (55/60) and 8.3% (5/60), respectively. Complete and incomplete resection rates were 96.6% (58/60) and 3.3% (2/60), respectively. Complications were major bleeding [n = 3 (5%)] and perforations [n = 5 (8.3%)] (4 colon, 1 stomach). Two patients with colonic perforations and two patients with submucosal lymphatic and microvasculature invasion (1 gastric carcinoid tumor, 1 colonic adenocarcinoma) were referred to surgery. During a mean follow-up of 12 mo, 1 patient with adenoma with high grade dysplasia underwent a second ESD procedure to resect a local recurrence. CONCLUSION: ESD is a feasible and safe method for treatment of premalignant lesions and early malignant gastrointestinal epithelial and subepithelial lesions. Successful en bloc and complete resection of lesions yield high cure rates with low recurrence.展开更多
Narrow band imaging(NBI) endoscopy is an optical image enhancing technology that allows a detailed inspection of vascular and mucosal patterns, providing the ability to predict histology during real-time endoscopy. By...Narrow band imaging(NBI) endoscopy is an optical image enhancing technology that allows a detailed inspection of vascular and mucosal patterns, providing the ability to predict histology during real-time endoscopy. By combining NBI with magnification endoscopy(NBI-ME), the accurate assessment of lesions in the gastrointestinal tract can be achieved, as well as the early detection of neoplasia by emphasizing neovascularization. Promising results of the method in the diagnosis of premalignant and malignant lesions of gastrointestinal tract have been reported in clinical studies. The usefulness of NBI-ME as an adjunct to endoscopic therapy in clinical practice, the potential to improve diagnostic accuracy, surveillance strategies and cost-saving strategies based on this method are summarized in this review. Various classification systems of mucosal and vascular patterns used to differentiate preneoplastic and neoplastic lesions have been reviewed. We concluded that the clinical applicability of NBI-ME has increased, but standardization of endoscopic criteria and classification systems, validation in randomized multicenter trials and training programs to improve the diagnostic performance are all needed before the widespread acceptance of the method in routine practice. However, published data regarding the usefulness of NBI endoscopy are relevant in order to recommend the method as a reliable tool in diagnostic and therapy, even for less experienced endoscopists.展开更多
Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis,due largely to late diagnosis.The importance of the interaction between Helicobacter pylori(H.pylori)infec...Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis,due largely to late diagnosis.The importance of the interaction between Helicobacter pylori(H.pylori)infection,the main risk factor,and host-related genetic factors has been studied intensively in recent years.The genetic predisposition for non-hereditary gastric cancer is difficult to assess,as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined.For non-cardiac intestinal-type cancer,identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies.The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H.pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia;the literature now includes various and non-conclusive results on this topic.The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions.Among the investigated gene variants onlyIL10T-819C,IL-8-251,IL-18RAP917997,IL-22 rs1179251,IL1-B-511,IL1-B-3954,IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk.One of the most important limiting factors is the inhomogeneity of the studies(e.g.,the lack of data on concomitant H.pylori infection,methods used to assess preneoplastic lesions,and source population).Testing the modifying effect of H.pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions,or even testing the interaction between H.pylori and cytokine gene variants in multivariable models adjusted for potential covariates,could increase generalizability of results.展开更多
With the recent upsurge of studies in the field of microbiology,we have learned more about the complexity of the gastrointestinal microecosystem.More than 30 genera and 1000 species of gastrointestinal microflora have...With the recent upsurge of studies in the field of microbiology,we have learned more about the complexity of the gastrointestinal microecosystem.More than 30 genera and 1000 species of gastrointestinal microflora have been found.The structure of the normal microflora is relatively stable,and is in an interdependent and restricted dynamic equilibrium with the body.In recent years,studies have shown that there is a potential relationship between gastrointestinal microflora imbalance and gastric cancer(GC)and precancerous lesions.So,restoring the balance of gastrointestinal microflora is of great significance.Moreover,intervention in gastric premalignant condition(GPC),also known as precancerous lesion of gastric cancer(PLGC),has been the focus of current clinical studies.The holistic view of traditional Chinese medicine(TCM)is consistent with the microecology concept,and oral TCM can play a two-way regulatory role directly with the microflora in the digestive tract,restoring the homeostasis of gastrointestinal microflora to prevent canceration.However,large gaps in knowledge remain to be addressed.This review aims to provide new ideas and a reference for clinical practice.展开更多
AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric lesions incl...AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia (IM) and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1 000 mg thrice daily for 3 mo. All patients underwent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy. Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay. RESULTS: The mean of folate concentration in gastric mucosa was 9.03±3.37 μg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83±3.02 μg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53 expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2 oncogene protein decreased after folic acid therapy. CONCLUSION: These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.展开更多
Aim To investigate the role of the Chinese herbal medicine Xianhuayin on the reversal of 7,12-dimethylbenz[a]anthracene (DMBA)-induced premalignant mucosal lesions in the oral buccal pouch of golden hamsters. Method...Aim To investigate the role of the Chinese herbal medicine Xianhuayin on the reversal of 7,12-dimethylbenz[a]anthracene (DMBA)-induced premalignant mucosal lesions in the oral buccal pouch of golden hamsters. Methodology The animals were randomly divided into a non-diseased control group (n=5) and an experimental group including 50 animals in which the buccal mucosa had been painted with DMBA (0.5% in acetone) to generate an oral mucosa premalignant lesion. Animals in the experi- mental group were further divided into Xianhuayin-treated group (n=30), untreated prem'alignant lesion group (n=10) and normal saline (NS)-treated group (n=10). The cheek (buccal) pouch mucosa of the golden hamsters in each group was observed with light and electron microscopy eight weeks after intragastric administration with NS or Xianhuayin. Results In the non-diseased control group, the buccal mucosa was keratinized and stratified squamous epithelium under a light microscope. In the untreated premalignant lesion group, variable degrees of epithelial dysplasia was observed. The irregular epithelial mucosa gradually became distinct in the Xianhuayin-treated group. Scanning electronic microscopic (SEM) analysis showed that surface of the cells exhibited honeycomb structures in the hamster of untreated- group. The cells were morphologically irregular, overlapped and loosened in the untreated premalignant lesion group. Most of the cell surface exhibited honeycomb structure in the Xianhuayin-treated group. Transmission electronic micro- scopic (TEM) analysis showed that buccal mucosal epithelial cells were morphologically regular in the non-diseased control group. Desmosomes and tonofibrils were reduced and the nucleus was morphologically irregular in the untreated premalignant lesion group. In the Xianhuayin-treated group, the widening intercellular gap was gradually reduced, desmosomes and the cells becoming morphologically regular. No significant difference was observed between the hamsters in N展开更多
Gastric cancer is the fifth most common cancer and in 2018,it was the third most common cause of cancer-related deaths worldwide.Endoscopic advances continue to be made for the diagnosis and management of both early g...Gastric cancer is the fifth most common cancer and in 2018,it was the third most common cause of cancer-related deaths worldwide.Endoscopic advances continue to be made for the diagnosis and management of both early gastric cancer and premalignant gastric conditions.In this review,we discuss the epidemiology and risk factors of gastric cancer and emphasize the differences in early vs latestage gastric cancer outcomes.We then discuss endoscopic advances in the diagnosis of early gastric cancer and premalignant gastric lesions.This includes the implementation of different imaging modalities such as narrow-band imaging,chromoendoscopy,confocal laser endomicroscopy,and other experimental techniques.We also discuss the use of endoscopic ultrasound in the diagnosis and staging of early gastric cancer.We then discuss the endoscopic advances made in the treatment of these conditions,including endoscopic mucosal resection,endoscopic submucosal dissection,and hybrid techniques such as laparoscopic endoscopic cooperative surgery.Finally,we comment on the current suggested recommendations for surveillance of both gastric cancer and its premalignant conditions.展开更多
Background Breast cancer has become one of the most common malignant tumors among females over the past several years.Breast carcinogenesis is a continuous process,which is featured by the normal epithelium progressin...Background Breast cancer has become one of the most common malignant tumors among females over the past several years.Breast carcinogenesis is a continuous process,which is featured by the normal epithelium progressing to premalignant lesions and then to invasive breast cancer (IBC).Targeting premalignant lesions is an effective strategy to prevent breast cancer.The establishment of animal models is critical to study the mechanisms of breast carcinogenesis,which will facilitate research on breast cancer prevention and drug behaviors.In this study,we established a feasible chemically-induced rat model of premalignant breast cancer.Methods Following the administration of the drugs (carcinogen,estrogen,and progestogen) to Sprague-Dawley (SD) rats,tumors or suspicious tumors were identified by palpation or ultrasound imaging,and were surgically excised for pathological evaluation.A series of four consecutive steps were carried out in order to determine the carcinogen:7,12-dimethylbenzaanthracene (DMBA) or 1-methyl-1-nitrosourea,the route of carcinogen administration,the administration period of estrogen and progestogen,and the DMBA dosage.Results Stable premalignant lesions can be induced in SD rats on administration of DMBA (15 mg/kg,administered three times) followed by administration of female hormones 5-day cycle.Results were confirmed by ultrasound and palpation.Conclusion Under the premise of drug dose and cycle,DMBA combined with estrogen and progestogen can be used as a SD rat model for breast premalignant lesions.展开更多
Gastric cancer(GC)is one of the most common malignancies globally,the occurrence of which undergoes a multistage chronic evolutionary process.It is a great public health issue to deeply understand the mechanisms of GC...Gastric cancer(GC)is one of the most common malignancies globally,the occurrence of which undergoes a multistage chronic evolutionary process.It is a great public health issue to deeply understand the mechanisms of GC development and factors affecting the evolution of gastric lesions.Helicobacter pylori infection has been identified as one of the main factors for gastric carcinogenesis and microbial dysbiosis.With the advances in molecular biology techniques,other gastric microbes besides H.pylori have been observed to play an essential role in the development of GC.Previous animal model studies suggested that specific and critical microbes in the stomach can accelerate the malignant transformation of gastric mucosa and the progression of gastric lesions to GC.Recently,the composition of human gastric microbiota has been investigated from stages of precancerous lesions to GC,including characteristics of gastric microbiota diversity,lesion-associated differential microbes,predicted microbiotarelated functions,microbiota interactions,and microbial mechanisms in gastric carcinogenesis.In this review,we provide an overview of the gastric microbiota,summarize current studies exploring the roles of microbiota in gastric carcinogenesis,and illustrate the significance and prospects of integrative multiomics analysis combined with the microbiome in gastric carcinogenesis.展开更多
Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibros...Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, and oral erythroplakia are the most common oral mucosal diseases that have a very high malignant transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaquelike, atrophic, erosive, and bullous type, clinically. Atrophic and erosive subtypes have the greater increased malignant transformation risk compared to another subtypes. Although there are various etiological studies, the etiology of almost all these diseases is not fully understood. Geographically, etiologic factors may vary.The most frequently reported possible factors are tobacco use, alcohol drinking, chewing of betel quid containing areca nut, and solar rays. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. For most diseases, treatment results are not satisfactory in spite of miscellaneous therapies. While at the forefront of surgical intervention, topical and systemic treatment alternatives such as corticosteroids, calcineurin inhibitors, and retinoids are widely used.展开更多
Background: incidence of Colorectal cancer (CRC) is increasing globally. In Egypt, CRC ranks the sixth most common cancer in males and the fifth in females. Aim: To assess the expression of estrogen receptors (alpha a...Background: incidence of Colorectal cancer (CRC) is increasing globally. In Egypt, CRC ranks the sixth most common cancer in males and the fifth in females. Aim: To assess the expression of estrogen receptors (alpha and beta) in pre-malignant (adenomatous polyps and IBD), malignant colorectal lesions and normal colonic mucosa in group of Egyptian patients. Methods: This prospective study was done on 45 patients presenting with colonic symptoms, patients were divided into four groups;15 CRC patients, 10 patients with adenomatous polyps, 10 IBD patients and 10 patients in the control group. Patients subjected to: Stool analysis, FOBT, CBC, CEA, Abdominal ultrasound & colonoscopy and biopsy (number = 80), Pathological, immunohistochemistry and RT- PCR quantification of ERα and ERβ were done. Results: Mean age: 39.2 (12 - 73), gender: M/F: 28/17. Bleeding per rectum was the commonest presentation;29/45 (64.4%). CEA was significantly elevated in the CRC group compared with other studied groups (1692 mg/L vs. 4.0, 4.0 and 4.4 mg/L). Ultrasonography of the studied patients showed that metastatic CRC: 3/15 (20%);Colonic wall thickening: 5/15 (33.3%), 1/10 showed colonic polypoidal lesions in adenomatous polyps groups, in IBD group: 4/10 (40%) showed colonic and ileocecal thicknening. All the studied patients showed negative results for estrogen receptors (alpha and beta) by the use of immunohistochemistry staining and RT-PCR technique. Conclusion: Role of estrogen receptors in the colonic mucosa, precancerous and colorectal cancer is doubtful, contradictory results with some literature data could be due to racial and genetic difference in the studied population.展开更多
Helicobacter pylori(H.pylori)gastritis may progress to high risk gastropathy and cancer.However,the pathological progression has not been characterized in detail.H.pylori induce persistent inflammatory infiltration.Ne...Helicobacter pylori(H.pylori)gastritis may progress to high risk gastropathy and cancer.However,the pathological progression has not been characterized in detail.H.pylori induce persistent inflammatory infiltration.Neutrophils are unique in that they directly infiltrate into foveolar epithelium aiming the proliferative zone specifically.Neutrophilic proliferative zone foveolitis is a critical pathogenic step in H.pylori gastritis inducing intensive epithelial damage.Epithelial cells carrying accumulated genomic damage and mutations show the Malgun(clear)cell change,characterized by large clear nucleus and prominent nucleolus.Malgun cells further undergo atypical changes,showing nuclear folding,coarse chromatin,and multiple nucleoli.The atypical Malgun cell(AMC)change is a novel premalignant condition in high risk gastropathy,which may progress and undergo malignant transformation directly.The pathobiological significance of AMC in gastric carcinogenesis is reviewed.A new diagnosis system of gastritis is proposed based on the critical pathologic steps classifying low and high risk gastritis for separate treatment modality.It is suggested that the regulation of H.pylori-induced neutrophilic foveolitis might be a future therapeutic goal replacing bactericidal antibiotics approach.展开更多
Evidence for the influence of chronic inflammation induced by microbial dysbiosis on aberrant DNA methylation supports a plausible connexion between disordered microbiota and precancerous lesions of gastric cancer(PLG...Evidence for the influence of chronic inflammation induced by microbial dysbiosis on aberrant DNA methylation supports a plausible connexion between disordered microbiota and precancerous lesions of gastric cancer(PLGC).Here,a comprehensive study including multi-omics data was performed to estimate the relationships amongst the gastric microbiome,inflammatory proteins and DNA methylation alterations and their roles in PLGC development.The results demonstrated that gastric dysbacteriosis increased the risk of PLGC and DNA methylation alterations in related tumour suppressor genes.Seven inflammatory biomarkers were identified for antrum and corpus tissues,respectively,amongst which the expression levels of several biomarkers were significantly correlated with the microbial dysbiosis index(MDI)and methylation status of specific tumour suppressor genes.Notably,mediation analysis revealed that microbial dysbiosis partially contributed to DNA methylation changes in the stomach via the inflammatory cytokines C-C motif chemokine 20(CCL20)and tumour necrosis factor receptor superfamily member 9(TNFRSF9).Overall,these results may provide new insights into the mechanisms that might link the gastric microbiome to PLGC.展开更多
The occurrence and development of esophageal cancer(EC)is a multi-stage process involving from inflammation to invasive cancer.However,this process is very complex,and so far there are few relevant studies to reveal t...The occurrence and development of esophageal cancer(EC)is a multi-stage process involving from inflammation to invasive cancer.However,this process is very complex,and so far there are few relevant studies to reveal this process.Early diagnosis and treatment of EC is the focus of the early diagnosis and treatment of malignant tumors project in China.How to screen EC in a lower cost and more efficient way deserves to be explored.Here,we reviewed the recent advances in the mechanisms of the occurrence and development,and early diagnosis and treatment of EC.展开更多
Objective: To evaluate the rate and types of human papillomavirus infection in vulvar intraepithelial neoplasia. Methods: We detected and identified HPV in 40 VIN cases with 67 lesions using PCR based reverse line b...Objective: To evaluate the rate and types of human papillomavirus infection in vulvar intraepithelial neoplasia. Methods: We detected and identified HPV in 40 VIN cases with 67 lesions using PCR based reverse line blot hybridization and DNA sequencing. Among the 40 patients, 13 were diagnosed as VIN Ⅲ, 11 as VIN Ⅱ, and 16 as VIN Ⅰ. 31 patients had multifocal disease. First a fragment of 150 bp was amplified from the L1 region of HPV with GPS/GP6 primers. If the result was negative, a short fragment of 65 bp was amplified also from the LI region with SPFI/SPF2 primers. Results: Using general primer GPS/GP6, the positive rate was 52.2% (35167). Using a short PCR fragment (SPF PCR), the positive rate of the rest 32 lesions was 81.2% (26132). The total positive rate was 91.0% (61/67). 90% of the HPV types found in VIN were high risk types. All 35 GP PCR products were analyzed by sequencing. The gene types of 31 mono-infection lesions were in accordance with the reverse line blot results, while sequence results of the 4 multi-infection samples could not be analyzed. The SPF PCR products were also sequenced, 24 of the 26 SPF PCR products could be analyzed and 2 samples failed. 80.6% (25/31) cases with multifocal VIN displayed the identical type of HPV, suggesting monoclonality in different lesions from the same patient. Conclusion: The high risk type of HPV is associated with vulvar intraepithelial neoplasia and may be necessary for development of HPV-associated invasive vulvar carcinoma.展开更多
AIM: To analyze the expression profiles of premalignant and/or preclinical lesions of gastric cancers.METHODS: We analyzed the expression profiles of normal gastric pit, tubular adenoma and carcinoma in situ using mic...AIM: To analyze the expression profiles of premalignant and/or preclinical lesions of gastric cancers.METHODS: We analyzed the expression profiles of normal gastric pit, tubular adenoma and carcinoma in situ using microdissected cells from routine gastric biopsies. For the DNA microarray analysis of formalin-fixed samples,we developed a simple and reproducible RNA extraction and linear amplification procedure applying two polymerasebinding sites. The amplification procedure took only 8 h and yielded comparable DNA microarray data between formalin-fixed tissues and unfixed controls.RESULTS: In comparison with normal pit, adenoma/carcinoma showed 504 up-regulated and 29 down-regulated genes at the expected false significance rate 0.15%. The differential expression between adenoma and carcinoma in situ was subtle: 50 and 22 genes were up-, and down-regulated in carcinomas at the expected false significance rate of 0.61%, respectively. Differentially expressed genes were grouped according to patterns of the sequential changes for the 'tendency analysis' in the gastric mucosaadenoma-carcinoma sequence.CONCLUSION: Groups of genes are shown to reflect the sequential expression changes in the early carcinogenic steps of stomach cancer. It is suggested that molecular carcinogenic pathways could be analyzed using routinely processed biopsies.展开更多
Objective: To investigate the expression of p16, cyclin D1 and Rb protein in gastric carcinoma and premalignant lesions including dysplastic gastric mucosa and intestinal metaplasia gastric mucosa. Methods: Using SP i...Objective: To investigate the expression of p16, cyclin D1 and Rb protein in gastric carcinoma and premalignant lesions including dysplastic gastric mucosa and intestinal metaplasia gastric mucosa. Methods: Using SP immunohistochemical methods, the expression of pl6, cyclin D1 and Rb proteins was detected in 10 specimens of normal gastric mucosa, 15 specimens of dysplastic gastric mucosa, 15 specimens of intestinal metaplasia gastric mucosa, 30 specimens of gastric carcinoma. The clinical characteristics of the 30 patients with gastric carcinoma were analysed to explore the relationship between the parameter detected and biological action of gastric cancer. Results: Expression of p16 protein was detected in 90% of normal gastric mucosa, 86.67% of dysplastic gastric mucosa, 86.67% of intestinal metaplasia gastric mucosa, 36.67% of gastric carcinoma. The positive rate of p16 protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.01). Expression of cyclin D1 protein was detected in 10% of normal gastric mucosa, 20% of dysplastic gastric mucosa, 20% of intestinal metaplasia gastric mucosa, 53.33% of gastric carcinoma. The positive rate of cyclin D1, protein expression in gastric carcinoma is significantly higher than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.05). Expression of Rb protein was detected in 90% of normal gastric mucosa, 80% of dysplastic gastric mucosa, 80% of intestinal metaplasia gastric mucosa, 50% of gastric carcinoma. The positive rate of Rb protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa (P<0.05). The expression of p16, cyclin D1 gene were associated with the degree of differentiation of gastric carcinoma, lymphnodes metastasis and distant metastasis. Conclusion: p16, Cyclin D1 and Rb gene play important role in gastric carcinoma genesis. The expression of p16, cyclin D1 and Rb gene have some value to the diagnosis at earl展开更多
In order to explore the role of telomerase activity (TA) in the development and progression of gastric cancer (GC) and if TA can be used as an indicator for the early diagnosis of GC, TA in 176 specimens of gastric mu...In order to explore the role of telomerase activity (TA) in the development and progression of gastric cancer (GC) and if TA can be used as an indicator for the early diagnosis of GC, TA in 176 specimens of gastric mucosa of 57 cases of chronic atrophic gastritis (CAG), 18 intestinal metaplasia (IM), 8 dysplasia (Dys), 65 GC obtained through operation or endoscopy was determined with PCR-based TRAP assay. Meanwhile, operative specimens of GC were analyzed with serial dilution. It was found that TA was detected in 24. 6% of CGA, 38. 9% of IM, 37.5% of Dys and 92.3% of GC, but not detected in 28 cases of normal tissues. TA detection was not related to patients’ sex, tumor location, size, depth of invasion, differentiation, lymph node metastasis and clinicalstage. Telomerase activity in premalignant lesions indicates that it plays a crucial role in the development and progression of GC. Thus the determination of telomerase activity is helpful to predict the progress of premalignant changes and to diagnose early GC.展开更多
文摘AIM: To investigate the indication, feasibility, safety, and clinical utility of endoscopic submucosal dissection (ESD) in the management of various gastrointestinal pathologies. METHODS: The medical records of 60 consecutive patients (34 female, 26 male) who underwent ESD at the gastroenterology department of Kocaeli University from 2006-2010 were examined. Patients selected for ESDhad premalignant lesions or non-invasive early cancers of the gastrointestinal tract and had endoscopic and histological diagnoses. Early cancers were considered to be confined to the submucosa, with no lymph node involvement by means of computed tomography and endosonography. RESULTS: Sixty ESD procedures were performed. The indications were epithelial lesions (n = 39) (33/39 adenoma with high grade dysplasia, 6/39 adenoma with low grade dysplasia), neuroendocrine tumor (n = 7), cancer (n = 7) (5/7 early colorectal cancer, 2/7 early gastric cancer), granular cell tumor (n = 3), gastrointestinal stromal tumor (n = 2), and leiomyoma (n = 2). En bloc and piecemeal resection rates were 91.6% (55/60) and 8.3% (5/60), respectively. Complete and incomplete resection rates were 96.6% (58/60) and 3.3% (2/60), respectively. Complications were major bleeding [n = 3 (5%)] and perforations [n = 5 (8.3%)] (4 colon, 1 stomach). Two patients with colonic perforations and two patients with submucosal lymphatic and microvasculature invasion (1 gastric carcinoid tumor, 1 colonic adenocarcinoma) were referred to surgery. During a mean follow-up of 12 mo, 1 patient with adenoma with high grade dysplasia underwent a second ESD procedure to resect a local recurrence. CONCLUSION: ESD is a feasible and safe method for treatment of premalignant lesions and early malignant gastrointestinal epithelial and subepithelial lesions. Successful en bloc and complete resection of lesions yield high cure rates with low recurrence.
文摘Narrow band imaging(NBI) endoscopy is an optical image enhancing technology that allows a detailed inspection of vascular and mucosal patterns, providing the ability to predict histology during real-time endoscopy. By combining NBI with magnification endoscopy(NBI-ME), the accurate assessment of lesions in the gastrointestinal tract can be achieved, as well as the early detection of neoplasia by emphasizing neovascularization. Promising results of the method in the diagnosis of premalignant and malignant lesions of gastrointestinal tract have been reported in clinical studies. The usefulness of NBI-ME as an adjunct to endoscopic therapy in clinical practice, the potential to improve diagnostic accuracy, surveillance strategies and cost-saving strategies based on this method are summarized in this review. Various classification systems of mucosal and vascular patterns used to differentiate preneoplastic and neoplastic lesions have been reviewed. We concluded that the clinical applicability of NBI-ME has increased, but standardization of endoscopic criteria and classification systems, validation in randomized multicenter trials and training programs to improve the diagnostic performance are all needed before the widespread acceptance of the method in routine practice. However, published data regarding the usefulness of NBI endoscopy are relevant in order to recommend the method as a reliable tool in diagnostic and therapy, even for less experienced endoscopists.
基金Supported by an Internal Research Grant from the University of Medicine,Pharmacy,Sciences and Technology of Targu Mure,No.615/12/17.01.2019
文摘Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis,due largely to late diagnosis.The importance of the interaction between Helicobacter pylori(H.pylori)infection,the main risk factor,and host-related genetic factors has been studied intensively in recent years.The genetic predisposition for non-hereditary gastric cancer is difficult to assess,as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined.For non-cardiac intestinal-type cancer,identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies.The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H.pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia;the literature now includes various and non-conclusive results on this topic.The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions.Among the investigated gene variants onlyIL10T-819C,IL-8-251,IL-18RAP917997,IL-22 rs1179251,IL1-B-511,IL1-B-3954,IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk.One of the most important limiting factors is the inhomogeneity of the studies(e.g.,the lack of data on concomitant H.pylori infection,methods used to assess preneoplastic lesions,and source population).Testing the modifying effect of H.pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions,or even testing the interaction between H.pylori and cytokine gene variants in multivariable models adjusted for potential covariates,could increase generalizability of results.
基金This work was supported by the Tianjin Sci-Tech Projects(No.16YFZCSY01070),China.
文摘With the recent upsurge of studies in the field of microbiology,we have learned more about the complexity of the gastrointestinal microecosystem.More than 30 genera and 1000 species of gastrointestinal microflora have been found.The structure of the normal microflora is relatively stable,and is in an interdependent and restricted dynamic equilibrium with the body.In recent years,studies have shown that there is a potential relationship between gastrointestinal microflora imbalance and gastric cancer(GC)and precancerous lesions.So,restoring the balance of gastrointestinal microflora is of great significance.Moreover,intervention in gastric premalignant condition(GPC),also known as precancerous lesion of gastric cancer(PLGC),has been the focus of current clinical studies.The holistic view of traditional Chinese medicine(TCM)is consistent with the microecology concept,and oral TCM can play a two-way regulatory role directly with the microflora in the digestive tract,restoring the homeostasis of gastrointestinal microflora to prevent canceration.However,large gaps in knowledge remain to be addressed.This review aims to provide new ideas and a reference for clinical practice.
基金Supported by the Science and Technology Foundation of the State Railway Ministry, No. J98Z034
文摘AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia (IM) and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1 000 mg thrice daily for 3 mo. All patients underwent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy. Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay. RESULTS: The mean of folate concentration in gastric mucosa was 9.03±3.37 μg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83±3.02 μg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53 expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2 oncogene protein decreased after folic acid therapy. CONCLUSION: These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.
基金supported by grants from the highly distinguished Oncology Subject Foundation of Colleges in Hebei Province
文摘Aim To investigate the role of the Chinese herbal medicine Xianhuayin on the reversal of 7,12-dimethylbenz[a]anthracene (DMBA)-induced premalignant mucosal lesions in the oral buccal pouch of golden hamsters. Methodology The animals were randomly divided into a non-diseased control group (n=5) and an experimental group including 50 animals in which the buccal mucosa had been painted with DMBA (0.5% in acetone) to generate an oral mucosa premalignant lesion. Animals in the experi- mental group were further divided into Xianhuayin-treated group (n=30), untreated prem'alignant lesion group (n=10) and normal saline (NS)-treated group (n=10). The cheek (buccal) pouch mucosa of the golden hamsters in each group was observed with light and electron microscopy eight weeks after intragastric administration with NS or Xianhuayin. Results In the non-diseased control group, the buccal mucosa was keratinized and stratified squamous epithelium under a light microscope. In the untreated premalignant lesion group, variable degrees of epithelial dysplasia was observed. The irregular epithelial mucosa gradually became distinct in the Xianhuayin-treated group. Scanning electronic microscopic (SEM) analysis showed that surface of the cells exhibited honeycomb structures in the hamster of untreated- group. The cells were morphologically irregular, overlapped and loosened in the untreated premalignant lesion group. Most of the cell surface exhibited honeycomb structure in the Xianhuayin-treated group. Transmission electronic micro- scopic (TEM) analysis showed that buccal mucosal epithelial cells were morphologically regular in the non-diseased control group. Desmosomes and tonofibrils were reduced and the nucleus was morphologically irregular in the untreated premalignant lesion group. In the Xianhuayin-treated group, the widening intercellular gap was gradually reduced, desmosomes and the cells becoming morphologically regular. No significant difference was observed between the hamsters in N
文摘Gastric cancer is the fifth most common cancer and in 2018,it was the third most common cause of cancer-related deaths worldwide.Endoscopic advances continue to be made for the diagnosis and management of both early gastric cancer and premalignant gastric conditions.In this review,we discuss the epidemiology and risk factors of gastric cancer and emphasize the differences in early vs latestage gastric cancer outcomes.We then discuss endoscopic advances in the diagnosis of early gastric cancer and premalignant gastric lesions.This includes the implementation of different imaging modalities such as narrow-band imaging,chromoendoscopy,confocal laser endomicroscopy,and other experimental techniques.We also discuss the use of endoscopic ultrasound in the diagnosis and staging of early gastric cancer.We then discuss the endoscopic advances made in the treatment of these conditions,including endoscopic mucosal resection,endoscopic submucosal dissection,and hybrid techniques such as laparoscopic endoscopic cooperative surgery.Finally,we comment on the current suggested recommendations for surveillance of both gastric cancer and its premalignant conditions.
文摘Background Breast cancer has become one of the most common malignant tumors among females over the past several years.Breast carcinogenesis is a continuous process,which is featured by the normal epithelium progressing to premalignant lesions and then to invasive breast cancer (IBC).Targeting premalignant lesions is an effective strategy to prevent breast cancer.The establishment of animal models is critical to study the mechanisms of breast carcinogenesis,which will facilitate research on breast cancer prevention and drug behaviors.In this study,we established a feasible chemically-induced rat model of premalignant breast cancer.Methods Following the administration of the drugs (carcinogen,estrogen,and progestogen) to Sprague-Dawley (SD) rats,tumors or suspicious tumors were identified by palpation or ultrasound imaging,and were surgically excised for pathological evaluation.A series of four consecutive steps were carried out in order to determine the carcinogen:7,12-dimethylbenzaanthracene (DMBA) or 1-methyl-1-nitrosourea,the route of carcinogen administration,the administration period of estrogen and progestogen,and the DMBA dosage.Results Stable premalignant lesions can be induced in SD rats on administration of DMBA (15 mg/kg,administered three times) followed by administration of female hormones 5-day cycle.Results were confirmed by ultrasound and palpation.Conclusion Under the premise of drug dose and cycle,DMBA combined with estrogen and progestogen can be used as a SD rat model for breast premalignant lesions.
基金Institutional Review Boards of Peking University Cancer Hospital and Institute(2021KT142).
文摘Gastric cancer(GC)is one of the most common malignancies globally,the occurrence of which undergoes a multistage chronic evolutionary process.It is a great public health issue to deeply understand the mechanisms of GC development and factors affecting the evolution of gastric lesions.Helicobacter pylori infection has been identified as one of the main factors for gastric carcinogenesis and microbial dysbiosis.With the advances in molecular biology techniques,other gastric microbes besides H.pylori have been observed to play an essential role in the development of GC.Previous animal model studies suggested that specific and critical microbes in the stomach can accelerate the malignant transformation of gastric mucosa and the progression of gastric lesions to GC.Recently,the composition of human gastric microbiota has been investigated from stages of precancerous lesions to GC,including characteristics of gastric microbiota diversity,lesion-associated differential microbes,predicted microbiotarelated functions,microbiota interactions,and microbial mechanisms in gastric carcinogenesis.In this review,we provide an overview of the gastric microbiota,summarize current studies exploring the roles of microbiota in gastric carcinogenesis,and illustrate the significance and prospects of integrative multiomics analysis combined with the microbiome in gastric carcinogenesis.
文摘Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, and oral erythroplakia are the most common oral mucosal diseases that have a very high malignant transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaquelike, atrophic, erosive, and bullous type, clinically. Atrophic and erosive subtypes have the greater increased malignant transformation risk compared to another subtypes. Although there are various etiological studies, the etiology of almost all these diseases is not fully understood. Geographically, etiologic factors may vary.The most frequently reported possible factors are tobacco use, alcohol drinking, chewing of betel quid containing areca nut, and solar rays. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. For most diseases, treatment results are not satisfactory in spite of miscellaneous therapies. While at the forefront of surgical intervention, topical and systemic treatment alternatives such as corticosteroids, calcineurin inhibitors, and retinoids are widely used.
文摘Background: incidence of Colorectal cancer (CRC) is increasing globally. In Egypt, CRC ranks the sixth most common cancer in males and the fifth in females. Aim: To assess the expression of estrogen receptors (alpha and beta) in pre-malignant (adenomatous polyps and IBD), malignant colorectal lesions and normal colonic mucosa in group of Egyptian patients. Methods: This prospective study was done on 45 patients presenting with colonic symptoms, patients were divided into four groups;15 CRC patients, 10 patients with adenomatous polyps, 10 IBD patients and 10 patients in the control group. Patients subjected to: Stool analysis, FOBT, CBC, CEA, Abdominal ultrasound & colonoscopy and biopsy (number = 80), Pathological, immunohistochemistry and RT- PCR quantification of ERα and ERβ were done. Results: Mean age: 39.2 (12 - 73), gender: M/F: 28/17. Bleeding per rectum was the commonest presentation;29/45 (64.4%). CEA was significantly elevated in the CRC group compared with other studied groups (1692 mg/L vs. 4.0, 4.0 and 4.4 mg/L). Ultrasonography of the studied patients showed that metastatic CRC: 3/15 (20%);Colonic wall thickening: 5/15 (33.3%), 1/10 showed colonic polypoidal lesions in adenomatous polyps groups, in IBD group: 4/10 (40%) showed colonic and ileocecal thicknening. All the studied patients showed negative results for estrogen receptors (alpha and beta) by the use of immunohistochemistry staining and RT-PCR technique. Conclusion: Role of estrogen receptors in the colonic mucosa, precancerous and colorectal cancer is doubtful, contradictory results with some literature data could be due to racial and genetic difference in the studied population.
基金Supported by Doyak Research Program(2009-79398)through National Research Foundation grant funded by the Ministry of science,ICT,and Future Planning
文摘Helicobacter pylori(H.pylori)gastritis may progress to high risk gastropathy and cancer.However,the pathological progression has not been characterized in detail.H.pylori induce persistent inflammatory infiltration.Neutrophils are unique in that they directly infiltrate into foveolar epithelium aiming the proliferative zone specifically.Neutrophilic proliferative zone foveolitis is a critical pathogenic step in H.pylori gastritis inducing intensive epithelial damage.Epithelial cells carrying accumulated genomic damage and mutations show the Malgun(clear)cell change,characterized by large clear nucleus and prominent nucleolus.Malgun cells further undergo atypical changes,showing nuclear folding,coarse chromatin,and multiple nucleoli.The atypical Malgun cell(AMC)change is a novel premalignant condition in high risk gastropathy,which may progress and undergo malignant transformation directly.The pathobiological significance of AMC in gastric carcinogenesis is reviewed.A new diagnosis system of gastritis is proposed based on the critical pathologic steps classifying low and high risk gastritis for separate treatment modality.It is suggested that the regulation of H.pylori-induced neutrophilic foveolitis might be a future therapeutic goal replacing bactericidal antibiotics approach.
基金funded by Grant of Science and Technology of Fujian,China(2019L3006)Special Funds of Fujian Finance Department(2020czbz01)High-level Talents Research Start-up Project of Fujian Medical University(XRCZX2017035 and XRCZX2020034).
文摘Evidence for the influence of chronic inflammation induced by microbial dysbiosis on aberrant DNA methylation supports a plausible connexion between disordered microbiota and precancerous lesions of gastric cancer(PLGC).Here,a comprehensive study including multi-omics data was performed to estimate the relationships amongst the gastric microbiome,inflammatory proteins and DNA methylation alterations and their roles in PLGC development.The results demonstrated that gastric dysbacteriosis increased the risk of PLGC and DNA methylation alterations in related tumour suppressor genes.Seven inflammatory biomarkers were identified for antrum and corpus tissues,respectively,amongst which the expression levels of several biomarkers were significantly correlated with the microbial dysbiosis index(MDI)and methylation status of specific tumour suppressor genes.Notably,mediation analysis revealed that microbial dysbiosis partially contributed to DNA methylation changes in the stomach via the inflammatory cytokines C-C motif chemokine 20(CCL20)and tumour necrosis factor receptor superfamily member 9(TNFRSF9).Overall,these results may provide new insights into the mechanisms that might link the gastric microbiome to PLGC.
文摘The occurrence and development of esophageal cancer(EC)is a multi-stage process involving from inflammation to invasive cancer.However,this process is very complex,and so far there are few relevant studies to reveal this process.Early diagnosis and treatment of EC is the focus of the early diagnosis and treatment of malignant tumors project in China.How to screen EC in a lower cost and more efficient way deserves to be explored.Here,we reviewed the recent advances in the mechanisms of the occurrence and development,and early diagnosis and treatment of EC.
文摘Objective: To evaluate the rate and types of human papillomavirus infection in vulvar intraepithelial neoplasia. Methods: We detected and identified HPV in 40 VIN cases with 67 lesions using PCR based reverse line blot hybridization and DNA sequencing. Among the 40 patients, 13 were diagnosed as VIN Ⅲ, 11 as VIN Ⅱ, and 16 as VIN Ⅰ. 31 patients had multifocal disease. First a fragment of 150 bp was amplified from the L1 region of HPV with GPS/GP6 primers. If the result was negative, a short fragment of 65 bp was amplified also from the LI region with SPFI/SPF2 primers. Results: Using general primer GPS/GP6, the positive rate was 52.2% (35167). Using a short PCR fragment (SPF PCR), the positive rate of the rest 32 lesions was 81.2% (26132). The total positive rate was 91.0% (61/67). 90% of the HPV types found in VIN were high risk types. All 35 GP PCR products were analyzed by sequencing. The gene types of 31 mono-infection lesions were in accordance with the reverse line blot results, while sequence results of the 4 multi-infection samples could not be analyzed. The SPF PCR products were also sequenced, 24 of the 26 SPF PCR products could be analyzed and 2 samples failed. 80.6% (25/31) cases with multifocal VIN displayed the identical type of HPV, suggesting monoclonality in different lesions from the same patient. Conclusion: The high risk type of HPV is associated with vulvar intraepithelial neoplasia and may be necessary for development of HPV-associated invasive vulvar carcinoma.
基金Supported by a Korea Research Foundation Grant, KRF-2003-041-E00052
文摘AIM: To analyze the expression profiles of premalignant and/or preclinical lesions of gastric cancers.METHODS: We analyzed the expression profiles of normal gastric pit, tubular adenoma and carcinoma in situ using microdissected cells from routine gastric biopsies. For the DNA microarray analysis of formalin-fixed samples,we developed a simple and reproducible RNA extraction and linear amplification procedure applying two polymerasebinding sites. The amplification procedure took only 8 h and yielded comparable DNA microarray data between formalin-fixed tissues and unfixed controls.RESULTS: In comparison with normal pit, adenoma/carcinoma showed 504 up-regulated and 29 down-regulated genes at the expected false significance rate 0.15%. The differential expression between adenoma and carcinoma in situ was subtle: 50 and 22 genes were up-, and down-regulated in carcinomas at the expected false significance rate of 0.61%, respectively. Differentially expressed genes were grouped according to patterns of the sequential changes for the 'tendency analysis' in the gastric mucosaadenoma-carcinoma sequence.CONCLUSION: Groups of genes are shown to reflect the sequential expression changes in the early carcinogenic steps of stomach cancer. It is suggested that molecular carcinogenic pathways could be analyzed using routinely processed biopsies.
文摘Objective: To investigate the expression of p16, cyclin D1 and Rb protein in gastric carcinoma and premalignant lesions including dysplastic gastric mucosa and intestinal metaplasia gastric mucosa. Methods: Using SP immunohistochemical methods, the expression of pl6, cyclin D1 and Rb proteins was detected in 10 specimens of normal gastric mucosa, 15 specimens of dysplastic gastric mucosa, 15 specimens of intestinal metaplasia gastric mucosa, 30 specimens of gastric carcinoma. The clinical characteristics of the 30 patients with gastric carcinoma were analysed to explore the relationship between the parameter detected and biological action of gastric cancer. Results: Expression of p16 protein was detected in 90% of normal gastric mucosa, 86.67% of dysplastic gastric mucosa, 86.67% of intestinal metaplasia gastric mucosa, 36.67% of gastric carcinoma. The positive rate of p16 protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.01). Expression of cyclin D1 protein was detected in 10% of normal gastric mucosa, 20% of dysplastic gastric mucosa, 20% of intestinal metaplasia gastric mucosa, 53.33% of gastric carcinoma. The positive rate of cyclin D1, protein expression in gastric carcinoma is significantly higher than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.05). Expression of Rb protein was detected in 90% of normal gastric mucosa, 80% of dysplastic gastric mucosa, 80% of intestinal metaplasia gastric mucosa, 50% of gastric carcinoma. The positive rate of Rb protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa (P<0.05). The expression of p16, cyclin D1 gene were associated with the degree of differentiation of gastric carcinoma, lymphnodes metastasis and distant metastasis. Conclusion: p16, Cyclin D1 and Rb gene play important role in gastric carcinoma genesis. The expression of p16, cyclin D1 and Rb gene have some value to the diagnosis at earl
文摘In order to explore the role of telomerase activity (TA) in the development and progression of gastric cancer (GC) and if TA can be used as an indicator for the early diagnosis of GC, TA in 176 specimens of gastric mucosa of 57 cases of chronic atrophic gastritis (CAG), 18 intestinal metaplasia (IM), 8 dysplasia (Dys), 65 GC obtained through operation or endoscopy was determined with PCR-based TRAP assay. Meanwhile, operative specimens of GC were analyzed with serial dilution. It was found that TA was detected in 24. 6% of CGA, 38. 9% of IM, 37.5% of Dys and 92.3% of GC, but not detected in 28 cases of normal tissues. TA detection was not related to patients’ sex, tumor location, size, depth of invasion, differentiation, lymph node metastasis and clinicalstage. Telomerase activity in premalignant lesions indicates that it plays a crucial role in the development and progression of GC. Thus the determination of telomerase activity is helpful to predict the progress of premalignant changes and to diagnose early GC.