Endoscopic submucosal dissection for premalignant lesions and noninvasive early gastrointestinal cancers

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.

EXPRESSION OF p16,CYCLIN D1 AND RB PROTEIN IN GASTRIC CARCINOMA AND PREMALIGNANT LESIONS

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 earlier stage of gastric cancer. Detection of expression of p16, cyclin D1 gene would be helpful to judge the prognosis of gastric cancer.

Significance of β-tubulin Expression in Breast Premalignant Lesions and Carcinomas

OBJECTIVE To explore the expression of β-tubulin in premalignant lesions and carcinomas of the breast, and to observe the relationship of its expression with breast cancer pathological features. METHODS The expression of β-tubulin was detected immunohistochemically in 50 specimens of premalignant lesions of the breast （ADH and Peri-PM with ADH）, 50 specimens of breast in situ ductal carcinomas （DCIS）, and 50 specimens of invasive ductal carcinomas （IDC）. Thirty specimens of normal breast tissues served as a control group. RESULTS Immunohistochemical analysis showed that： the differences among the 4 groups （normal breast tissues, breast premalignant lesions, DCIS and IDC, P 〈 0.05） were significant, and there were also statistically significant differences between any 2 groups （P 〈 0.05） except for the β-tubulin positive expression comparing DCIS versus IDC （P 〉 0.05）. In addition, β-tubulin was expressed at a higher level in Peri-PM with ADH compared to ADH （P 〈 0.05）. Following the degree of breast epithelial hyperplasia involved, and its development into carcinoma, the β-tubulin positive expression displayed an elevating tendency. We also found a significant positive relationship of β-tubulin expression with lymph node metastasis （P 〈 0.05）, but no significant correlation with histological grading and nuclear grade. CONCLUSION Centrosome defects may be an early event in the development of breast cancer and they can also promote tumor progression. Studies of aberrations of centrosomal proteins provide a new way to tumorigenesis. explore the mechanism of breast tumorigenesis.

Inflammation as a Mediator of Microbiome Dysbiosis-Associated DNA Methylation Changes in Gastric Premalignant Lesions

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.

Effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in premalignant gastric lesions

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.

Role of the Chinese Herbal Medicine Xianhuayin on the Reversal of Premalignant Mucosal Lesions in the Golden Hamster Buccal Pouch

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 NS-treated group and those in the untreated premalignant lesion group. Significant therapeutic efficacy was observed in the group receiving Xianhuayin. Conclusion Xianhuayin is effective in the reversal of DMBA-induced premalignant lesions in the buccal pouch of golden hamsters.

Precancerous lesions of oral mucosa

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.

Screening for Oral Cancer 2018

In Hungary, the incidence and mortality from oral cancer is so high, that in the past decades it has attracted international attention. The mortality rates are the highest in Europe. As risk factors, smoking and alcohol drinking have a multiplicative role;in addition, a number of dental factors also play a role. Premalignant conditions and lesions are well known. They should be targeted for early detection and early treatment. The screening tool is simple: inspection and palpation. The physician-patient encounters provide opportunity for screening. This paper looks for the answer to the long debated question: who is responsible for oral screening?

Gene expression profiling reveals sequential changes in gastric tubular adenoma and carcinoma in situ

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.

Intraductal papillary neoplasm of the bile duct developing in a patient with primary sclerosing cholangitis: A case report

We report a case of intraductal papillary neoplasm of the bile duct(IPNB) that developed in a patient with primary sclerosing cholangitis. A 46-year-old woman was admitted to our hospital with obstructive jaundice. The liver function tests demonstrated increased serum liver enzyme levels. Computed tomography showed dilatation of the intrahepatic bile ducts. Abdominal ultrasonography revealed a highly echoic protruding lesion in the posterior bile duct near the right lobe of the liver. The lesion was suspected to be IPNB, but we were unable to confirm whether it was a carcinoma. A right hepatectomy was performed, and this showed that the dilated bile duct was filled with mucin and contained several yellowish papillary tumors. Histologically, the neoplastic biliary epithelium showed papillary growth in the dilated lumen. The tumor was diagnosed as IPNB, high-grade intraepithelial neoplasia secreting abundant mucin. No recurrence has been detected 3 years after surgery.

Circulating immune parameters-based nomogram for predicting malignancy in laryngeal neoplasm

BACKGROUND Malignancy prediction remains important to preoperative diagnosis and postoperative follow-up in laryngeal neoplasm.AIM To evaluate the circulating immune population and develop a nomogram for prediction of malignancy in patients with laryngeal neoplasm.METHODS A primary cohort of 156 patients was divided into laryngeal benign lesion,premalignant lesion and malignant lesion groups.Peripheral blood from patients was measured by blood routine test and flow cytometry.A nomogram was developed and applied to a validation cohort containing 55 consecutive patients.RESULTS Age,gender and seven circulating immune parameters exhibited significant differences between laryngeal benign lesion and premalignant lesion.The nomogram incorporated predictors,including gender,age,smoke index,proportions of monocytes,CD8+T cells,CD4+T cells,B cells and CD4/CD8+T cell ratio.It showed good discrimination between laryngeal premalignant lesion and malignant lesion,with a C-index of 0.844 for the primary cohort.Application of this nomogram in the validation cohort(C-index,0.804)still had good discrimination and good calibration.Decision curve analysis revealed that the nomogram was clinically useful.CONCLUSION This novel nomogram,incorporating both clinical risk factors and circulating immune parameters,could be appropriately applied in preoperative individualized prediction of malignancy in patients with laryngeal neoplasm.

Gastric microbiota and its role in gastric carcinogenesis

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.

The role of computer-assisted systems for upper-endoscopy quality monitoring and assessment of gastric lesions

This article analyses the literature regarding the value of computer-assisted systems in esogastroduodenoscopy-quality monitoring and the assessment of gastric lesions.Current data show promising results in upper-endoscopy quality control and a satisfactory detection accuracy of gastric premalignant and malignant lesions,similar or even exceeding that of experienced endoscopists.Moreover,artificial systems enable the decision for the best treatment strategies in gastriccancer patient care,namely endoscopic vs surgical resection according to tumor depth.In so doing,unnecessary surgical interventions would be avoided whilst providing a better quality of life and prognosis for these patients.All these performance data have been revealed by numerous studies using different artificial intelligence(AI)algorithms in addition to white-light endoscopy or novel endoscopic techniques that are available in expert endoscopy centers.It is expected that ongoing clinical trials involving AI and the embedding of computer-assisted diagnosis systems into endoscopic devices will enable real-life implementation of AI endoscopic systems in the near future and at the same time will help to overcome the current limits of the computer-assisted systems leading to an improvement in performance.These benefits should lead to better diagnostic and treatment strategies for gastric-cancer patients.Furthermore,the incorporation of AI algorithms in endoscopic tools along with the development of large electronic databases containing endoscopic images might help in upper-endoscopy assistance and could be used for telemedicine purposes and second opinion for difficult cases.

Recent advances in the mechanisms of development and the early diagnosis and treatment of esophageal cancer

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.