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Background: Microbiota may be associated with esophageal squamous cell carcinoma (ESCC) development. However, it is not known the predictive value of microbial biomarkers combining epidemiological factors for the early detection of ESCC and precancerous lesions. Methods: A total of 449 specimens (esophageal swabs and saliva) were collected from 349 participants with different esophageal statuses in China to explore and validate ESCC-associated microbial biomarkers from genes level to species level by 16S rRNA sequencing, metagenomic sequencing and real-time quantitative polymerase chain reaction. Results: A bacterial biomarker panel including Actinomyces graevenitzii (A.g_1, A.g_2, A.g_3, A.g_4), Fusobacteria nucleatum (F.n_1, F.n_2, F.n_3), Haemophilus haemolyticus (H.h_1), Porphyromonas gingivalis (P.g_1, P.g_2, P.g_3) and Streptococcus australis (S.a_1) was explored by metagenomic sequencing to early detect the participants in Need group (low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and ESCC) vs participants without these lesions as the Noneed group. Significant quantitative differences existed for each microbial target in which the detection efficiency rate was higher in saliva than esophageal swab. In saliva, the area under the curve (AUC) based on the microbial biomarkers (A.g_4 ∩ P.g_3 ∩ H.h_1 ∩ S.a_1 ∩ F.n_2) was 0.722 (95% CI 0.621–0.823) in the exploration cohort. Combining epidemiological factors (age, smoking, drinking, intake of high-temperature food and toothache), the AUC improved to 0.869 (95% CI 0.802–0.937) in the exploration cohort, which was validated with AUC of 0.757 (95% CI 0.663–0.852) in the validation cohort. Conclusions: It is feasible to combine microbial biomarkers in saliva and epidemiological factors to early detect ESCC and precancerous lesions in China. [ABSTRACT FROM AUTHOR]

Background: Although endoscopic screening for esophageal cancer has been performed in high‐risk areas in China for decades, there is limited and inconsistent evidence regarding the starting age for individuals participating in screening. The aim of this study is to investigate the optimal starting age of esophageal cancer screening. Methods: This study is based on a multicenter prospective cohort consisting 338,017 permanent residents aged 40–69 years in six high‐risk areas of esophageal cancer in China. The participation rate, detection rate, hazard ratios (HRs), cumulative incidence and mortality and number needed to screen (NNS) were calculated in each age group. Screening burden, benefit and risk were compared among screening strategies with different initiation ages to explore the optimal starting age for population‐based screening in high‐risk areas. Results: Individuals aged 50–69 had a higher participation rate, a higher detection rate and improved screening effectiveness than those aged 40–49. The endoscopic screening had no significant effect on reducing the incidence of esophageal cancer in individuals under 55 and mortality in individuals under 45. Increasing the starting age to 50 years reduced the screening demand and NNS by 40% and 55%, and resulted in 12% of detectable positive cases, 16% of preventable incident cases, and 14% of preventable deaths being missed. Conclusions: Postponing the starting age of endoscopic screening to 50 years might yield a more‐favorable balance between screening benefit and burden in high‐ risk areas with limited resources. [ABSTRACT FROM AUTHOR]

In our study, we aimed to assess the long‐term risk of gastric cardia adenocarcinoma (GCA) for patients with different histological cardia lesions to inform future guidelines for GCA screening in China. We conducted a population‐based prospective study among 9740 subjects who underwent upper endoscopy screening during 2005 to 2009 and followed until December 2017. Cumulative incidence and mortality rates of GCA were calculated by the baseline histological diagnoses, and the hazard ratios (HRs), overall and by age and sex, were analyzed by Cox proportional hazards models. During a median follow‐up of 10 years, we identified 123 new GCA cases (1.26%) and 31 GCA deaths (0.32%). The age‐standardized incidence and mortality rates of GCA were 128.71/100 000 and 35.69/100 000 person‐years, and cumulative incidence rate in patients with cardia high‐grade dysplasia (CHGD), cardia low‐grade dysplasia (CLGD) and atrophic carditis (AC)/cardia intestinal metaplasia (CIM) was 25%, 3.05% and 1.58%, respectively. The progression rate and cancer risk of GCA increased monotonically with each step in Correa's cascade. Individuals aged 50 to 69 years had 4.4 times higher GCA incidence than those aged 40 to 49 years. Patients with CLGD had a significantly higher 3‐year GCA incidence than the normal group, while patients with AC/CIM had a comparable GCA risk during 3‐year follow‐up but a higher risk at 5‐year intervals. Our results suggested a postponed starting age of 50 years for GCA screening, immediate treatment for patients with CHGD, a 3‐year surveillance interval for patients with CLGD, and a lengthened surveillance interval of 5 years for patients with AC/CIM. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) has a high incidence rate and poor prognosis. In this study, we aimed to develop a predictive model to estimate the individualized 5-year absolute risk for ESCC in Chinese populations living in the high-risk areas of China. Methods: We developed a risk-predicting model based on the epidemiologic data from a population-based case-control study including 244 newly diagnosed ESCC patients and 1,220 healthy controls. Initially, we included easy-to-obtain risk factors to construct the model using the multivariable logistic regression analysis. The area under the ROC curves (AUC) with cross-validation methods was used to evaluate the performance of the model. Combined with local age- and sex-specific ESCC incidence and mortality rates, the model was then used to estimate the absolute risk of developing ESCC within 5 years. Results: A relative risk model was established that included eight factors: age, sex, tobacco smoking, alcohol drinking, education, and dietary habits (intake of hot food, intake of pickled/salted food, and intake of fresh fruit). The relative risk model had good discrimination [AUC, 0.785; 95% confidence interval (CI), 0.749–0.821]. The estimated 5-year absolute risk of ESCC for individuals varied widely, from 0.0003% to 19.72% in the studied population, depending on the exposure to risk factors. Conclusions: Our model based on readily identifiable risk factors showed good discriminative accuracy and strong robustness. And it could be applied to identify individuals with a higher risk of developing ESCC in the Chinese population, who might benefit from further targeted screening to prevent esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) is widely accepted to be the most important cause of gastric non-cardia adenocarcinoma (GNCA), while its role in the development of gastric cardia adenocarcinoma (GCA) is not well-defined. We aimed to investigate current H. pylori infection in relation to the severity of both precancerous and cancerous lesions of the gastric cardia in an Asian population at high risk of GCA. Methods: A population-based cross-sectional study was conducted in Linzhou County, Henan Province, China. Two thousand three (2,003) randomly selected participants with data on current H. pylori infection, assayed by 13C-urea breath test (13C-UBT), and a sequence of histological diagnoses of the gastric cardia mucosa were analyzed. Results: Of 2,003 subjects, 828 (41.33%) were currently infected with H. pylori. The prevalence of current H. pylori infection increased with increasing severity of histological lesions, from 34.12% in subjects with normal gastric cardia mucosa to 52.17% in subjects with gastric cardia high-grade intraepithelial neoplasia (CHIN)/ gastric cardia adenocarcinoma (GCA) (P for trend <0.001). With H. pylori -negative subjects as the reference category, H. pylori -positive subjects had statistically significant elevated adjusted prevalence odds ratios (PORs) for each of the histological lesions. The PORs (95% CI) were 2.15 (1.74–2.64), 3.46 (2.08–5.75), 2.78 (1.90–4.07), and 3.05 (1.30–7.17) for subjects with carditis, cardia intestinal metaplasia (CIM), cardia low-grade intraepithelial neoplasia (CLIN), and CHIN/GCA), respectively. The associations remained when subjects with abnormal stomach non-cardia mucosa were excluded. Conclusions: This large epidemiologic study demonstrates a positive association between current H. pylori infection and the severity of both precancerous and cancerous lesions of the gastric cardia in an Asian population at high risk of GCA. These findings suggest that H. pylori infection may play a role throughout both early- and late-stage development of GCA. [ABSTRACT FROM AUTHOR]

Introduction: Prediction models for esophageal squamous cell carcinoma (ESCC) need to be proven effective in the target population before they can be applied to population-based endoscopic screening to improve cost-effectiveness. We have systematically reviewed ESCC prediction models applicable to the general population and performed external validation and head-to-head comparisons in a large multicenter prospective cohort including 5 high-risk areas of China (Fei Cheng, Lin Zhou, Ci Xian, Yang Zhong, and Yan Ting)., Methods: Models were identified through a systematic review and validated in a large population-based multicenter prospective cohort that included 89,753 participants aged 40-69 years who underwent their first endoscopic examination between April 2017 and March 2021 and were followed up until December 31, 2022. Model performance in external validation was estimated based on discrimination and calibration. Discrimination was assessed by C-statistic (concordance statistic), and calibration was assessed by calibration plot and Hosmer-Lemeshow test., Results: The systematic review identified 15 prediction models that predicted severe dysplasia and above lesion (SDA) or ESCC in the general population, of which 11 models (4 SDA and 7 ESCC) were externally validated. The C-statistics ranged from 0.67 (95% confidence interval 0.66-0.69) to 0.70 (0.68-0.71) of the SDA models, and the highest was achieved by Liu et al (2020) and Liu et al (2022). The C-statistics ranged from 0.51 (0.48-0.54) to 0.74 (0.71-0.77), and Han et al (2023) had the best discrimination of the ESCC models. Most models were well calibrated after recalibration because the calibration plots coincided with the x = y line., Discussion: Several prediction models showed moderate performance in external validation, and the prediction models may be useful in screening for ESCC. Further research is needed on model optimization, generalization, implementation, and health economic evaluation., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Objectives: To estimate the effectiveness of endoscopic screening programme in reducing incidence and mortality of upper gastrointestinal cancer in high risks areas of China., Design: This multicentre population-based cohort study was conducted in six areas in China from 2005 to 2015. All permanent residents aged 40 to 69 years were identified as target subjects. We refer to those who were invited for screening collectively as the invited group. Of these, we classify those who were invited and undertook endoscopic screening as the screened group and those who were invited but did not accept screening as the non-screened group. Target subjects who were not invited to the screening were assigned to the control group. The effectiveness of the endoscopic screening and screening programme were evaluated by comparing reductions in incidence and mortality from upper gastrointestinal cancer in the screened and invited group with control group., Results: Our cohort analysis included 637 500 people: 299 483 in the control group and 338 017 in the invited to screening group, 113 340 (33.53%) of whom were screened eventually. Compared with subjects in the control group, upper gastrointestinal cancer incidence and mortality decreased by 23% (relative risk (RR)=0.77, 95% CI 0.74 to 0.81) and 57% (RR=0.43, 95% CI 0.40 to 0.47) in the screened group, respectively, and by 14% (RR=0.86, 95% CI 0.84 to 0.89) and 31% (RR=0.69, 95% CI 0.66 to 0.72) in the invited group, respectively., Conclusion: Among individuals aged 40 to 69 years in high risk areas of upper gastrointestinal cancer, one-time endoscopic screening programme was associated with a significant decrease in upper gastrointestinal cancer incidence and mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To understand the distribution of esophageal squamous cell cancer and precursor lesions in high-risk areas of China, and to provide evidence for determining the reference ranges of detection rates in high-risk areas., Methods: Endoscopy with Lugol's iodine staining was performed on 15 709 local residents aged 40 to 69 years old in Linzhou of Henan province and Feicheng of Shandong province from 2005-2009. 35 cases without accurate pathology diagnosis and 11 cases with vital disease before screening were excluded. 15 663 subjects were enrolled in this study. Compliance was calculated by the percentage of the people who had endoscopic screening among the target population. Chi-square test and trend chi-square test were used to compare the distribution differences in age, gender and areas of esophageal squamous cell cancer and precancer. 95% CI of the detection rates was then employed to represent the reference ranges of esophageal squamous cell cancer and precursor lesions., Results: The compliance rate of screening endoscopy of this study was 49.36% (15 709/31 826) of all, and female's compliance (54.05%, 8 447/15 628) was much higher than that of male (44.83%, 7 262/16 198) (χ(2) = 88.14, P < 0.001). The detection rates of basal cell hyperplasia, low grade intraepithelial neoplasia, high grade intraepithelial neoplasia and esophageal squamous cell cancer of males were 4.17% (302/7 246), 17.22% (1 248/7 246), 1.67% (121/7 246), 0.83% (60/7 246), and were higher than that of females (3.45% (290/8 417), 14.82% (1 247/8 417), 1.41% (119/8 417), 0.48% (40/8 417), respectively). Except for high-grade intraepithelial neoplasia, the detection rates of male were higher than that of female (P values were 0.018, < 0.001, 0.960, 0.006). The detection rates of all grades of precursor lesions increased with age rising (all P values < 0.001), among which the detection rates of the mentioned four lesions for 40-44 years old were 2.69% (94/3 500), 8.11% (284/3 500), 0.40% (14/3 500), 0.14% (5/3 500), and that of 65-69 years old were 5.46% (46/843), 23.25% (196/843), 3.68% (31/843), 2.14% (18/843). The proportion of esophageal precursor lesion of Linzhou were higher than that of Feicheng observably except for esophageal squamous cell cancer (P values were < 0.001, < 0.001, < 0.001, 0.437). The detection rates of the four lesions of Linzhou and Feicheng were 4.90% (504/10 287), 17.37% (1 787/10 287), 1.79% (184/1 0287), 0.60% (62/10 287) and 1.64% (88/5 376), 13.17% (708/5 376), 1.04% (56/5 376), 0.71% (38/5 376). The 95% CI of detection rates of various lesions were, 3.78% (3.48%-4.08%) for basal cell hyperplasia, 15.93% (15.37%-16.50%) for low-grade intraepithelial neoplasia, 12.31% (11.79%-12.82%) for mild dysplasia and 3.62% (3.33%-3.91%) for moderate hyperplasia, 1.53% (1.34%-1.72%) for high-grade intraepithelial neoplasia and 0.64% (0.51%-0.76%) for esophageal squamous cell cancer, respectively., Conclusion: Up to 21.88% residents that were asymptomatic were suffered from esophageal squamous cancer or precursor lesions in high-risk areas in China. The distribution of esophageal squamous cell cancer and precursor lesions was closely related to the gender and the age, which suggested that males were supposed to be paid more attention to.

Objective: Endoscopy was used to study the high incidence area of cancer of gastric cardia., Methods: 417 patients with early cardiac cancer and 451 patients with advanced lesions were analyzed to the high incidence point of cardiac cancer. Verifying endoscopic screening of 205 subjects was performed later in the high incidence area of esophageal cancer., Results: 327 of 417 (78.4%) of early cardiac cancer patients and 336 of 451 (74.5%) of advanced lesions were proved to have developed their origin at the root of the mucosal fold in the gastric cardia. Eleven cardiac cancer patients were found by the verifying endoscopic screening, among whom 9 patients (81.8%) developed the primary focus at the root of mucosal fold in the cardia., Conclusion: The root of mucosal fold in the gastric cardia is proved to be the high incidence point of cancer of gastric cardia, which is very important clinically.