The incidence of esophageal adenocarcinoma (EAC) has increased in recent decades, and its 5-year survival rate is less than 20%. As a well-established precursor, patients with Barrett's esophagus (BE) have a persistent risk of progression to EAC. Many researchers have already identified some factors that may contribute to the development of BE and EAC, and the identified risks include gastroesophageal reflux (GER), male sex, older age, central obesity, tobacco smoking, Helicobacter pylori ( H. pylori ) eradication, and the administration of proton pump inhibitors (PPIs) and antibiotics. The human gut harbors trillions of microorganisms, the majority of which are bacteria. These microorganisms benefit the human host in many ways, such as helping in digestion, assisting in the synthesis of certain vitamins, promoting the development of the gastrointestinal immune system, regulating metabolism and preventing invasion by specific pathogens. In contrast, microbial dysbiosis may play important roles in various diseases, such as inflammation and cancers. The composition of the microbiota located in the normal esophagus is relatively conserved without distinct microbial preferences in the upper, middle and lower esophagus. Six major phyla constitute the esophageal microbiota, including Firmicutes , Bacteroides , Actinobacteria , Proteobacteria , Fusobacteria and TM7 , similar to the oral microbiota. Streptococcus dominates the esophageal microbiota. However, the microbiota varies in different esophageal diseases compared to that in the healthy esophagus. The type I microbiota, which is primarily composed of gram-positive bacteria, is closely associated with the normal esophagus, while type II microbiota has enriched gram-negative bacteria and is mainly associated with the abnormal esophagus. These increased gram-negative anaerobes/microaerophiles include Veillonella , Prevotella , Haemophilus , Neisseria , Granulicatella and Fusobacterium , many of which are associated with BE. The microbial diversity in the esophagus is decreased in EAC patients, and Lactobacillus fermentum is enriched compared to that in controls and BE patients. Furthermore, the microbiota may be associated with BE and EAC by interacting with their risk factors, including central obesity, GER, H. pylori , administration of PPIs and antibiotics. Therefore, a large gap in research must be bridged to elucidate the associations among these factors. Some studies have already proposed several potential mechanisms by which the microbiota participates in human carcinogenesis by complicated interactions with the human host immune system and signaling pathways. The activa...

A retrospective study was carried out to evaluate the diagnostic accuracy and the factors influencing the diagnostic accuracy of 648 procedures of ultrasound-guided percutaneous needle biopsy (PNB) for peripheral pulmonary lesions (PPLs). We reviewed the histopathology results, the clinical records and the procedure reports of these 648 biopsies and the final diagnoses of 637 PPLs to determine the diagnostic accuracy of ultrasound-guided PNB. Factors that influenced the diagnostic accuracy were assessed by analysis of the biopsy procedures, which were classified as diagnostic cases (true-positive and true-negative) and non-diagnostic cases (false-positive, false-negative and indeterminate). Statistical analyses of factors that related to patient demographic characteristics, lesion characteristics and biopsy details were performed to determine possible effects on diagnostic accuracy. Biopsies were successfully performed in all cases, and 11 patients underwent second biopsies for the same lesions. Among the 637 PPLs, there were 326 (51.2%) malignant lesions, 272 (42.7%) benign lesions and 39 (6.1%) indeterminate lesions. Of the 272 benign lesions, 114 (41.9%) were found to be tuberculous. The overall diagnostic accuracy was 81.8%, and the rates of hemoptysis, symptomatic pneumothorax and chest-tube insertion were 8.0%, 1.7% and 0.9%, respectively. Lesions sizes were divided into 3 groups according to the measurement by ultrasound. For lesions that measured ≤20 mm, 21-49 mm and ≥50 mm, the diagnostic accuracy was 72.0%, 86.8% and 79.7%, while sensitivity and specificity were 54.3%-79.2%, 88.3%-90.7% and 79.4%-89.5% and 77.3%-100%, 96.8%-100% and 58.6%-100%, respectively. Diagnostic accuracy was significantly affected by lesion size when lesion size was measured by ultrasound (p = 0.006) and computed tomography (CT) (p = 0.001). In the 3 lesion groups of ≤20 mm, 21-49 mm or ≥50 mm, diagnostic accuracy among each group was significantly different (p <0.001). When lesion size was measured by ultrasound (p <0.001) and CT (p <0.001) and the 3 groups were analyzed (p <0.001), there was a statistically significant relationship between lesion size and the presence of necrosis. The rates of the presence of necrosis in lesions that measured ≤20 mm, 21-49 mm and ≥50 mm were 3.9%, 11.7% and 28.8%, respectively. No significance was found for age (p = 0.119), gender (p = 0.25), lesion location (p = 0.55), the presence of necrosis (p = 0.226), patient position (p = 0.25), needle size (p = 0.26), puncture angle (p = 0.34) and needle passes (p = 0.21). Ultrasound-guided PNB is an effective and safe diagnostic method for PPLs; the diagnostic accuracy is significantly affected by lesion size and decreases in smaller (≤20 mm) and larger (≥50 mm) lesions.

BACKGROUNDEsophageal adenocarcinoma (EAC) is an aggressive disease with high mortality and an overall 5-year survival rate of less than 20%. Barrett’s esophagus (BE) is the only known precursor of EAC, and patients with BE have a persistent and excessive risk of EAC over time. Individuals with BE are up to 30-125 times more likely to develop EAC than the general population. Thus, early detection of EAC and BE could significantly improve the 5-year survival rate of EAC. Due to the limitations of endoscopic surveillance and the lack of clinical risk stratification strategies, molecular biomarkers should be considered and thoroughly investigated.AIMTo explore the transcriptome changes in the progression from normal esophagus (NE) to BE and EAC.METHODSTwo datasets from the Gene Expression Omnibus (GEO) in NCBI Database (https://www.ncbi.nlm.nih.gov/geo/) were retrieved and used as a training and a test dataset separately, since NE, BE, and EAC samples were included and the sample sizes were adequate. This study identified differentially expressed genes (DEGs) using the R/Bioconductor project and constructed trans-regulatory networks based on the Transcriptional Regulatory Element Database and Cytoscape software. Enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) terms was identified using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources. The diagnostic potential of certain DEGs was assessed in both datasets.RESULTSIn the GSE1420 dataset, the number of up-regulated DEGs was larger than that of down-regulated DEGs when comparing EAC vs NE and BE vs NE. Among these DEGs, five differentially expressed transcription factors (DETFs) displayed the same trend in expression across all the comparison groups. Of these five DETFs, E2F3, FOXA2, and HOXB7 were up-regulated, while PAX9 and TFAP2C were down-regulated. Additionally, the majority of the DEGs in trans-regulatory networks were up-regulated. The intersection of these potential DEGs displayed the same direction of changes in expression when comparing the DEGs in the GSE26886 dataset to the DEGs in trans-regulatory networks above. The receiver operating characteristic curve analysis was performed for both datasets and found that TIMP1 and COL1A1 could discriminate EAC from NE tissue, while REG1A, MMP1, and CA2 could distinguish BE from NE tissue. DAVID annotation indicated that COL1A1 and MMP1 could be potent biomarkers for EAC and BE, respectively, since they participate in the majority of the enriched KEGG and GO terms that are important for inflammation and cancer.CONCLUSIONAfter the construction and analyses of the trans-regulatory networks in EAC and BE, the results indicate that COL1A1 and MMP1 could be potential biomarkers for EAC and BE, respectively.