Human microbial communities are highly complex ecosystems, but it remains unclear if microbial compositions have any similarity in distinct sites of the oral cavity and esophagus in particular. Clinical samples were collected from three niches (saliva, tongue dorsum and supragingival plaque) of the oral cavity and three segments (upper, middle, and lower) of the esophagus in 27 healthy individuals. Bacterial V3-V4 region of 16S rRNA gene in these samples was amplified and sequenced on Illumina sequencing platform, followed by data analysis using QIIME and LEfSe softwares. Highly diverse bacterial flora with 365 genera belonging to 29 phyla resided in the oral cavity and 594 genera belonging to 29 phyla in the esophagus. The phyla Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria, and TM7 were most abundant in both the oral cavity and the esophagus, but the phyla Actinobacteria and Bacteroidetes were preferable in the oral cavity and Firmicutes in the esophagus. The genera Streptococcus, Neisseria, Prevotella, Actinobacillus, and Veillonella were most abundant in both oral cavity and esophagus, but Neisseria was preferable in the oral cavity and Streptococcus in the esophagus. Different niche-specific bacterial signatures were found in the oral cavity, e.g., the class Flavobacteria in the supragingival plaque, class Bacteroides in the saliva and the class Clostridia in the tongue dorsum. By contrast, no site specific bacteria for three different segments of esophagus were found. However, high variability of microbial compositions between individuals was observed. In conclusion, this study confirmed microbial diversity at different taxonomic levels in healthy oral cavity and esophagus, and identified the site-preferable bacterial signatures in six niches of the upper digestive tract. These findings provide a critical baseline for future studies interpreting microbiome-related diseases.

IntroductionOesophageal cancer (OC) is one of the most common cancers worldwide and about 50% of all new cases occurred in China. Population-based screening has been conducted in high-risk areas in China since 1970s, however, a few factors have limited the integration of the results from previous studies and the sharing of existing resources, such as the difference in screening methods and protocols, inconsistencies in questionnaires for risk factors investigation, lack of standards for sample collection and incomplete follow-up information.Methods and analysisThe National Cohort of Esophageal Cancer-Prospective Cohort Study of Esophageal Cancer and Precancerous Lesions based on High-Risk Population (NCEC-HRP) is a prospective cohort study of OC screening based on high-risk population in China supported by the National Key R&D Programme. Eight areas located at eastern, central and western China are selected as screening centres to represent three economical-geographical regions. All local residents aged 40–69 years in the selected areas are invited to take endoscopic examination and risk factors investigation unless they meet the exclusion criteria. The recruitment began on June 2017 and a total of 100 000 participants will be enrolled by December 2020 and all subjects will be followed for a long time. This study is designed as open-ended and has broad research aims. Summary statistics for baseline information will be reported after the completion of recruitment. We will develop a series of standards and guidelines for OC screening during the study. An open and shared research platform linked with epidemiological databases and biobank will be built up for further research.Ethics and disseminationThe study is approved by the Ethics Committee of Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (approval number 16-171/1250). The findings of the study will be disseminated through scientific peer-reviewed journals as well as the public via the study website (http://www.ncec-china.cn).Trial registration numberChiCTR-EOC-17010553; Pre-results.

Objective To evaluate the feasibility of DNA image cytometry (DNA-ICM) as a primary screening method for esophageal squamous cell cancer (ESCC). Methods A total of 5,382 local residents aged 40–69 years from three high-risk areas in China (Linzhou in Henan province, Feicheng in Shandong province and Cixian in Hebei province) from 2008 to 2011 were recruited in this population-based screening study. And 2,526 subjects declined to receive endoscopic biopsy examination with Lugol’s iodine staining, while 9 and 815 subjects were excluded from liquid-based cytology and DNA-ICM test respectively due to slide quality. Finally, 2,856, 5,373 and 4,567 subjects were enrolled in the analysis for endoscopic biopsy examination, liquid-based cytology and DNA-ICM test, respectively. Sensitivity (SE), specificity (SP), negative predictive values (NPV) and positive predictive values (PPV) as well as their 95% confidence intervals (95% CI) for DNA-ICM, liquid-based cytology and the combination of the two methods were calculated. Receiver operating characteristic (ROC) curves were applied to determine the cutoff point of DNA-ICM for esophageal cancer. Results DNA-ICM results were significantly correlative with esophageal cancer and precancer lesions (χ2=18.016, P<0.001). The cutoff points were 5,802, 5,803 and 8,002 based on dissimilar pathological types of low grade intraepithelial neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), and ESCC, respectively, and 5,803 was chosen in this study considering the SE and SP. The SE, SP, PPV, NPV of DNA-ICM test (cutoff point 5,803) combined with liquid-based cytology [threshold atypical squamous cells of undetermined significance (ASCUS)] were separately 72.1% (95% CI: 70.3%-73.9%), 43.3% (95% CI: 41.3%-45.3%), 22.8% (95% CI: 21.1%-24.5%) and 87.0% (95% CI: 85.7%-88.3%) for LGIN, 85.7% (95% CI: 84.3%-87.1%), 41.3% (95% CI: 39.3%-43.3%), 4.6% (95% CI: 3.8%-5.4%) and 98.9% (95% CI: 98.5%-99.3%) for HGIN, and 96.0% (95% CI: 95.2%-96.8%), 40.8% (95% CI: 38.8%-42.8%), 1.7% (95% CI: 1.2%-2.2%) and 99.9% (95% CI: 99.8%-100.0%) for ESCC. Conclusions It is possible to use DNA-ICM test as a primary screening method before endoscopic screening for esophageal cancer.

Background: Increasing attention has been devoted to cancer screening and microbiota in recent decades, but currently there is less focus on microbiota characterization among screeners and its relationship to anxiety and depression.Methods: We characterized the microbial communities of fecal samples collected through the FOBT card from anxiety and depression screeners and paired controls in Henan, China (1:2, N = 69). DNA was extracted using the MOBIO PowerSoil kit. The V4 region of the 16S rRNA gene was sequenced using MiniSeq and processed using QIIME1. LEfSe was used to identify differentially abundant microbes, the Wilcoxon rank-sum test was used to test alpha diversity differences, and permutational multivariate analysis of variance was used to test for differences in beta diversity.Results: Similar fecal microbiota signatures in composition were found among screeners. The intestinal microbial environments by phylum were all composed primarily of Firmicutes, Bacteroidetes, and Proteobacteria, and the corresponding top genera were Faecalibacterium, Roseburia, and Prevotella. Compared with controls, the ranking of the top five genera in the anxiety and depression group changed, and the dominant genus was Prevotella in the anxiety and depression group and Faecalibacterium in the control group. There was a lower relative abundance of Gemmiger (1.4 vs. 2.3%, P = 0.025), Ruminococcus (0.6 vs. 0.8%, P = 0.037), and Veillonella (0.6 vs. 1.3%, P = 0.020). This may be linked to the lower alpha diversity in participants with anxiety and depression (Observed OTUs: 122.35 vs. 143.24; Chao1: 127.35 vs. 149.98), although no significant differences were observed. Distinct clustering in microbial composition between the two groups was detected for the Jaccard distance (P = 0.011).Conclusions: Our study showed differing microbial characterization among participants with anxiety and depression in the endoscopic screening of upper gastrointestinal cancer. Gemmiger, Ruminococcus, and Veillonella were informative and have potential clinical implications, which need to be confirmed by large-scale, prospective cohort studies and biological mechanism research.

Objective Research on generalized anxiety disorder (GAD) and its association with esophageal cancer (EC) is sparse. The study aimed to explore the association between GAD and EC. Methods A multicenter, population‐based study in high‐risk regions for EC (ECHRRs) was conducted from 2017 to 2019. All participants received free endoscopy screening. If the esophageal endoscopy results were suspicious, the pathological biopsy was performed to confirm normal, esophagitis, low‐grade intraepithelial neoplasia (LGIN), high‐grade intraepithelial neoplasia (HGIN), and EC. Information on participants' exposure to risk factors was collected. GAD was assessed with Generalized Anxiety Disorder Scale‐7. Results With esophageal endoscopy, 25,650 participants in ECHRRs were examined, 9586 of whom were suspicious and confirmed by esophageal pathology. The detection rate of EC and precancerous lesions was 6.83% (1751/25,650), with 1377 LGIN (5.37%), 272 HGIN (1.06%), and 102 EC (0.40%) cases. The overall mean GAD score (95% CI) and prevalence among 25,650 participants with endoscopy were 1.96 (1.93–1.99) and 16.90%, respectively. The mean GAD score and prevalence among 9586 participants with pathology were 1.96 (1.91–2.02) and 17.98%, respectively. The mean GAD scores of patients confirmed with normal, esophagitis, LGIN, HGIN, and EC were 1.73 (1.62–1.85), 1.91 (1.85–1.97), 1.94 (1.80–2.08), 3.98 (3.73–4.23). and 2.97 (2.49–3.45), respectively (p < 0.001). The corresponding prevalence of GAD were 5.21%, 18.72%, 17.72%, 43.75%, and 36.27%, respectively (p < 0.001). The age‐ and gender‐adjusted odds ratios (ORs) between GAD and each esophageal lesion type were 1.02 (0.99–1.04), 1.01 (0.98–1.04), 1.27 (1.21–1.33), and 1.16 (1.08‐1.24), respectively. The ORs (95% CIs) of the positive associations were 1.08 (1.05–1.12), 1.03 (0.99–1.07), 1.35 (1.29–1.42), and 1.19 (1.10–1.29) after further adjustment for potential confounders (all p < 0.001). Sensitivity analysis showed that the positive association persisted. Conclusions GAD was significantly higher in patients with EC and precancerous lesions. Focusing on and alleviating anxiety in high‐risk groups (including patients with HGIN and EC) may be an effective strategy for EC prevention and control. Further prospective studies are warranted to validate the results.

Objective To explore the natural history of severe dysplasia/carcinoma in situ (SD/CIS) patients and to evaluate the efficacy of endoscopic treatment to SD/CIS patients. Methods Between January 2005 and December 2009, a population-based prospective screening program on esophageal squamous cell carcinoma (ESCC) was performed in Linzhou, China, with endoscopic screening plus iodine staining. All the eligible histologically confirmed SD/CIS patients were followed up through the door-to-door follow-up and local cancer registry. The endpoint was diagnosed as ESCC or the December 31st, 2016. Kaplan-Meier survival analysis and Log-rank test were used to compare the survival rates among treated and untreated patients. Results A total of 175 SD/CIS patients were enrolled and grouped by whether they received endoscopic treatment. Eleven-year cumulative incidence rates for untreated and treated SD/CIS patients were 10.7% [95% confidence interval (95% CI): 6.9−16.1] and 3.2% (95% CI: 1.4−7.0), respectively. The ESCC incidence free survival rate, and all-cause incidence and mortality free survival rates were all significantly higher in the treated patients vs. untreated patients (P=0.043, P=0.008 and P=0.015, respectively). The ESCC mortality free survival rate showed no significant differences between the two groups (P=0.847). Conclusions The cumulative incidence rate of SD/CIS patients to ESCC was much lower than previously reported. The Kaplan-Meier survival analysis showed that endoscopic treatment could increase the ESCC and all-cause disease-free survival rates of SD/CIS patients significantly.

did the conception and design of the study. Hao Feng, Guohui Song, and Wenqiang Wei carried out the provision of study materials or patients. Hao Feng,

Background Anastomotic leakage (AL) is one of the severe postoperative adverse events (5%-30%), and it is related to increased medical costs in cancer patients who undergo esophagectomies. Machine learning (ML) methods show good performance at predicting risk for AL. However, AL risk prediction based on ML models among the Chinese population is unavailable. Objective This study uses ML techniques to develop and validate a risk prediction model to screen patients with emerging AL risk factors. Methods Analyses were performed using medical records from 710 patients who underwent esophagectomies at the National Clinical Research Center for Cancer between January 2010 and May 2015. We randomly split (9:1) the data set into a training data set of 639 patients and a testing data set of 71 patients using a computer algorithm. We assessed multiple classification tools to create a multivariate risk prediction model. Our ML algorithms contained decision tree, random forest, naive Bayes, and logistic regression with least absolute shrinkage and selection operator. The optimal AL prediction model was selected based on model evaluation metrics. Results The final risk panel included 36 independent risk features. Of those, 10 features were significantly identified by the logistic model, including aortic calcification (OR 2.77, 95% CI 1.32-5.81), celiac trunk calcification (OR 2.79, 95% CI 1.20-6.48), forced expiratory volume 1% (OR 0.51, 95% CI 0.30-0.89); TLco (OR 0.56, 95% CI 0.27-1.18), peripheral vascular disease (OR 4.97, 95% CI 1.44-17.07), laparoscope (OR 3.92, 95% CI 1.23-12.51), postoperative length of hospital stay (OR 1.17, 95% CI 1.13-1.21), vascular permeability activity (OR 0.46, 95% CI 0.14-1.48), and fat liquefaction of incisions (OR 4.36, 95% CI 1.86-10.21). Logistic regression with least absolute shrinkage and selection operator offered the highest prediction quality with an area under the receiver operator characteristic of 72% in the training data set. The testing model also achieved similar high performance. Conclusions Our model offered a prediction of AL with high accuracy, assisting in AL prevention and treatment. A personalized ML prediction model with a purely data-driven selection of features is feasible and effective in predicting AL in patients who underwent esophagectomy.