Nuclear-cytoplasmic translocation of SQSTM1/p62 protein enhances ESCC cell migration and invasion by stabilizing EPLIN expression.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant disease with a poor prognosis. We previously found that p62 presented a marked nuclear-cytoplasmic translocation in ESCC cells as compared that in normal esophageal epithelial cells, but its effects on ESCC cells remain unclear. This study aims to clarify the impacts of different cellular localization of p62 on the function of ESCC cells and the underlying molecular mechanisms. We here demonstrated that cytoplasmic p62 enhances the migration and invasion abilities of esophageal cancer cells, whereas nuclear p62 has no effect. We further explored the interaction protein of p62 by using GST pull-down experiment and identified EPLIN as a potential protein interacting with p62. In addition, reducing EPLIN expression significantly inhibited the migration and invasion of ESCC cells, which were rescued when EPLIN expression was restored after the p62 knockdown. At a molecular level, p62 in cytoplasm positively regulated the expression of EPLIN via enhancing its protein stability. Data from the TCGA and GEO database displayed a significant up-regulation of EPLIN mRNA expression in ESCC tissues compared with corresponding paired esophageal epithelial samples. Our findings present evidence that the nuclear-cytoplasmic translocation of p62 protein contributes to an aggressive malignancy phenotype, providing candidate molecular biomarkers and potential molecular targets for the diagnosis and treatment of ESCC.

Geographic, sex and socioeconomic disparities in esophageal cancer incidence in China: A population-based study.

Geographic and sex differences in esophageal cancer have been reported in China, but data are lacking at the local level. We aimed to investigate geographic and sex disparities in esophageal cancer incidence among Chinese counties and whether county-level socioeconomic status was associated with these variations. We obtained esophageal cancer data from 2015 to 2017 for 782 counties from population-based cancer registries in China. We calculated age-standardized incidence rates and male-to-female incidence rate ratios (IRRs) by county. We performed hotspot analysis to identify geographical clusters. We used negative binomial regression models to analyze the association between incidence rates and county-level socioeconomic factors. There were significant geographic disparities in esophageal cancer incidence, with 8.1 times higher rate in the 90th-percentile county than in the 10th-percentile county (23.7 vs 2.9 per 100 000 person-years). Clusters of elevated rates were prominent across north-central China. Nationally, men had 2.9 times higher incidence of esophageal cancer than women. By county, the male-to-female IRRs ranged from 1.1 to 21.1. Clusters of high male-to-female IRRs were observed in northeast China. Rurality (IRR 1.16, 95% CI 1.10-1.22), per capita gross domestic product (IRR 0.95, 0.92-0.98) and percentage of people with a high school diploma (IRR 0.86, 0.84-0.87) in a county were significantly associated with esophageal cancer incidence. The male-to-female IRRs were higher in counties with higher socioeconomic status. Substantial differences in incidence rates and sex ratios of esophageal cancer exist between Chinese counties, and county-level socioeconomic status was associated with these variations. These findings may inform interventions to reduce these disparities.

Performance of Prediction Models for Esophageal Squamous Cell Carcinoma in General Population: A Systematic Review and External Validation Study.

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.

Plant-based dietary patterns and risk of esophageal cancer: A prospective cohort study spanning 17 years.

Objective: Plant-based diets have multiple health benefits for cancers; however, little is known about the association between plant-based dietary patterns and esophageal cancer (EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC. Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) of EC across 3 plant-based diet indices and further stratified the analysis by subgroups. Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365 person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50 (95% CI, 0.32-0.77) for hPDI. In addition, the HR per 10-point increase in the hPDI score was 0.42 (95% CI, 0.27-0.66) for ECs. Conversely, uPDI was positively associated with the risk of EC, and the HR was 1.80 (95% CI, 1.16-2.82). The HR per 10-point increase in the uPDI score was 1.90 (95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses. Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

The survival of esophageal cancer by subtype in China with comparison to the United States.

Adenocarcinoma (AC) and squamous cell carcinoma (SCC) are the main subtypes of esophageal cancer (EC), but nationwide survival of both EC subtypes has never been reported in China. Our study aimed to estimate the survival trends of EC by subtype in China and compare them with those in the United States for the same period. We used data from 64 Chinese cancer registries, which included EC patients diagnosed during 2008 and 2015 and followed up until 31st December 2017. The 5-year age-standardized relative survival by subtype, sex, age group and urban or rural area between 2008 and 2017 were analyzed. We stratified survival estimates by calendar period (2008-2009, 2010-2011, 2012-2014 and 2015-2017). Data from the SEER 18 program were calculated to estimate the survival of EC in the United States. A further comparison between the survivals in areas covered and not covered by population-based endoscopic screening programs in China was conducted. A total of 129 962 records were included in the survival analyses. Results revealed that age-standardized 5-year relative survivals for AC and SCC increased in both China and the United States from 2008 to 2017. In 2015 to 2017, 5-year survival from both subtypes in China was better than the United States (SCC: 36.9% vs 18.5%, AC: 34.8% vs 22.3%). The survival for both subtypes was significantly higher in screening areas than in nonscreening areas in China (SCC: 40.6% vs 32.8%; AC: 43.0% vs 31.3%). A survival gap in EC by subtype exists between China and the United States. Our results may support the beneficial effect of population-based endoscopic screening for survival, and may be poised to inform national policy-making in both countries.

The occurence of cancer in ageing populations at global and regional levels, 1990 to 2019.

BACKGROUND: population ageing contributes to increased cancer cases and deaths and has profound implications for global healthcare systems. We estimated the trends of cancer cases and deaths in ageing populations at global and regional levels. METHODS: using data from the Global Burden of Disease Study 2019, we analysed the change in cancer cases and deaths associated with population ageing, population growth and epidemiological factors from 1990 to 2019 using decomposition analysis. Additionally, we estimated the proportions of people aged 65 years and over accounting for total cases and deaths, and investigated relationships between the proportions and the Sociodemographic Index (SDI) using the Pearson correlation coefficient. RESULTS: from 1990 to 2019, there was an increase of 128.9% for total cases and 74.8% for total deaths in all cancers combined; the percentages of older people increased from 48.6% to 56.4% for cases and from 52.0% to 61.9% for deaths. Population ageing contributed to the largest increase in global cancer occurrence, with 56.5% for cases and 63.3% for deaths. However, the changes attributed to epidemiological factors was 5.2% for cancer cases and -33.4% for cancer deaths. The proportions of total cases and deaths of older adults were positively correlated with socioeconomic development of the country. CONCLUSION: our findings revealed that the main contributor to increased cancer cases and deaths has changed from comprehensive epidemiological factors to demographic shifts. To respond to the rapidly growing occurrence of cancer in ageing populations, the global health priority should focus on meeting the rising demand for cancer diagnosis, treatment and care services for older people.

Global and national trends in the age-specific sex ratio of esophageal cancer and gastric cancer by subtype.

A male predominance was observed in esophageal and gastric cancers, though present limited data has revealed variations by age. We aim to investigate the global age-specific sex differences in esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Data on esophageal and gastric cancers incidence by diagnosis year, sex, histology, subsite and age group were extracted from 171 registries in 54 countries included in the last two volumes (X and XI, 2003-2012) of Cancer Incidence in Five Continents, which contributing to over 80% of the global burdens of these cancers. Age-standardized incidence rates (ASIRs) and male-to-female ASIRs ratios were estimated for esophageal and gastric cancers, by histological subtype and subsite, globally and by country. We consistently observed a male predominance in esophageal and gastric cancers across the world from 2003 to 2012, with male-to-female ASIRs ratios of 6.7:1 for EAC, 3.3:1 for ESCC, 4.0:1 for GCC and 2.1:1 for GNCC. The sex differences were consistent across time periods but varied significantly by age across the life span. Across the four cancer types, the male-to-female incidence rate ratios increased from young ages, approaching a peak at ages 60-64, but sharply declined thereafter. Similar "low-high-low" trends of age-specific sex ratio were observed in other digestive cancers including liver, pancreas, colon and rectum with peak ages ranging from 50 to 65. Age-dependent risk factors warrant further investigation to aid our understanding of the underlying etiologies of esophageal and gastric cancers by histological subtype and subsite.

Dysregulation of CXCL14 promotes malignant phenotypes of esophageal squamous carcinoma cells via regulating SRC and EGFR signaling.

The present study was to identify abnormal methylation genes implicated in esophageal squamous cell carcinoma (ESCC). Genomic methylation alterations in ESCC tissues were analyzed using laser-microdissection and whole-genome bisulfite sequencing. CXCL14 promoter was frequently hypermethylated in ESCC tissues. The correlation of CXCL14 hypermethylation status and the mRNA and protein expression levels were validated using nested methylation-specific PCR (nMS-PCR), RNAscope in situ hybridization (RISH) and Western blot. RISH results showed completely negative CXCL14 expression in 34.3% (34/99) ESCC, compared with those in the basal layer cells of normal epithelia. Low expression of CXCL14 was more present in patients with lower differentiation. The anticancer role of CXCL14 has been commonly associated with immune regulation in the literature. Here, we observed by functional analysis that CXCL14 can also act as a tumor suppressor in ESCC cells. 5-Aza-dC treatment suppressed CXCL14 methylation and up-regulated the expression of CXCL14. Ectopic expression of CXCL14 suppressed the proliferation, invasion, tumor growth, and lung metastasis of ESCC cells. Both ectopic expression and induction of CXCL14 with 5-Aza-dC inhibited the activity of SRC, MEK1/2 and STAT3 in ESCC cells, while activated EGFR. Importantly, a combination of CXCL14 expression and SRC or EGFR inhibitor dramatically repressed the proliferation of ESCC cells and the growth of xenografts. Our findings revealed a direct tumor suppressor role of CXCL14, but not through the immune system. The data suggest that for ESCC patients with low level CXCL14, increasing CXCL14 expression combined with inhibition of SRC or EGFR might be a promising therapeutic strategy.

Genetic variant in miR-17-92 cluster binding sites is associated with esophageal squamous cell carcinoma risk in Chinese population.

BACKGROUND: Single nucleotide polymorphisms (SNPs) located in microRNA (miRNA) binding sites can affect the interactions between miRNAs and target genes, which is related to cancer susceptibility and tumorigenesis. However, the association between SNPs located in miR-17-92 cluster binding sites and ESCC risk remains unclear. Therefore, we aimed to explore the relationship between polymorphisms in miR-17-92 cluster binding sites and ESCC susceptibility. METHODS: Six SNPs in the binding sites of miR-17-92 cluster were selected using bioinformatics databases, and their association with ESCC risk was investigated in a case-control study (including 488 cases and 512 controls) based on the population from high incidence areas of ESCC in China. We evaluated the SNP-SNP and SNP-smoking interactions using generalized multifactor dimensionality reduction (GMDR). Moreover, the expression of the miR-17-92 cluster and its target genes was determined in ESCC and adjacent normal tissues by quantitative real-time polymerase chain reaction (qRT-PCR). The dual-luciferase reporter assay was conducted to verify the effect of SNPs on the binding affinity between miRNAs and target genes. RESULTS: We found that the SNP rs1804506 C > T had a significant association with the decreased ESCC risk. The SNP rs1804506 T allele was associated with a significantly decreased risk of ESCC in the additive model (OR = 0.817, 95% CI = 0.681-0.981, P = 0.030). The rs1804506 T allele had more striking effects on reducing ESCC risk in older individuals, female or non-smoker subgroups. We also found a significant interaction effect between rs1366600 and smoking by GMDR methods (P = 0.011). Additionally, the expression levels of miR-19a-3p and TGFBR3 were significantly downregulated in ESCC tissues compared with normal tissues, and the carriers of rs1804506 TT genotype had lower expression level of TGFBR3 than those of rs1804506 CC/CT genotype. Following dual-luciferase reporter assay showed that the rs1804506 T allele reduced the binding of miR-19a-3p and TGFBR3 3'-UTR. CONCLUSIONS: Our findings suggest that the rs1804506 polymorphism in miR-17-92 cluster binding sites contributes to the susceptibility of ESCC, which might provide new clues and scientific evidence for the etiology and biomarkers for the prevention and treatment of ESCC.

Processing body (P-body) and its mediators in cancer.

In recent years, processing bodies (P-bodies) formed by liquid-liquid phase separation, have attracted growing scientific attention due to their involvement in numerous cellular activities, including the regulation of mRNAs decay or storage. These cytoplasmic dynamic membraneless granules contain mRNA storage and decay components such as deadenylase and decapping factors. In addition, different mRNA metabolic regulators, including m6A readers and gene-mediated miRNA-silencing, are also associated with such P-bodies. Cancerous cells may profit from these mRNA decay shredders by up-regulating the expression level of oncogenes and down-regulating tumor suppressor genes. The main challenges of cancer treatment are drug resistance, metastasis, and cancer relapse likely associated with cancer stem cells, heterogeneity, and plasticity features of different tumors. The mRNA metabolic regulators based on P-bodies play a great role in cancer development and progression. The dysregulation of P-bodies mediators affects mRNA metabolism. However, less is known about the relationship between P-bodies mediators and cancerous behavior. The current review summarizes the recent studies on P-bodies mediators, their contribution to tumor development, and their potential in the clinical setting, particularly highlighting the P-bodies as potential drug-carriers such as exosomes to anticancer in the future.

Satisfaction in population-based cancer screening in a Chinese rural high-risk population: the Yangzhong early diagnosis and treatment of upper gastrointestinal cancer.

BACKGROUND: Screening for upper gastrointestinal cancer (UGC) effectively reduces morbidity and mortality in gastric and esophageal cancers. It is considered one of the effective measures for cancer control in China, but studies on its functional quality are lacking. Our study assessed the quality of screening service funded by Upper Gastrointestinal Cancer Early diagnosis and treatment (UGCEDAT) and its correlation in Yangzhong People's hospital, China. METHODS: A cross-sectional study was conducted among 516 screening users at a screening centre in Yanghzong People's hospital from April to July 2021. The service quality questionnaire (SERVQUAL) based on the service quality gap (SQG) model was adopted. We calculated the mean scores of perceptions and expectations and their gap. To determine the association between overall SQG and related features of participants, we used a multivariate logistic regression. RESULTS: The average scores of screening service users' perceptions and expectations were 4.05 and 4.55, respectively. The SQG of five dimensions (tangibles, reliability, responsiveness, assurance and empathy) were negative, and the overall SQG was -0.51. The responsiveness dimension had the largest gap, and tangibles had the smallest gap. Occupation status (AOR: 0.57; CI: 0.37-0.89), health self-assessment (AOR: 4.97; CI: 1.35-18.23), endoscopy experience (AOR: 0.55; CI: 0.38-0.81), distance from screening hospital (AOR: 1.85; CI: 1.25-2.73) and frequency of visit (AOR: 1.65; CI: 1.10-2.46) were associated with the overall SQG. CONCLUSIONS: We observed a negative gap between perceptions and expectations of the function quality of screening service, implying a high dissatisfaction across different dimensions. Service providers should take adequate measures to bridge the dimension with the largest quality gap. Meanwhile, attention should be paid to identifying the influencing factors of the overall SQG and the characteristics of dimensional expectations and perceptions to improve the effectiveness of the screening program.

Design and Fabrication of a Novel Wheel-Ring Triaxial Gyroscope.

This paper presents a new type of three-axis gyroscope. The gyroscope comprises two independent parts, which are nested to further reduce the structure volume. The capacitive drive was adopted. The motion equation, capacitance design, and spring design of a three-axis gyroscope were introduced, and the corresponding formulas were derived. Furthermore, the X/Y driving frequency of the gyroscope was 5954.8 Hz, the Y-axis detection frequency was 5774.5 Hz, and the X-axis detection frequency was 6030.5 Hz, as determined by the finite element simulation method. The Z-axis driving frequency was 10,728 Hz, and the Z-axis sensing frequency was 10,725 Hz. The MEMS gyroscope's Z-axis driving mode and the sensing mode's frequency were slightly mismatched, so the gyroscope demonstrated a larger bandwidth and higher Z-axis mechanical sensitivity. In addition, the structure also has good Z-axis impact resistance. The transient impact simulation of the gyroscope structure showed that the maximum stress of the sensitive structure under the impact of 10,000 g@5 ms was 300.18 Mpa. The gyroscope was produced by etching silicon wafers in DRIE mode to obtain a high aspect ratio structure, tightly connected to the glass substrate by silicon/glass anode bonding technology.

Demonstration of quasi-real-time intrafractional motion in esophageal cancer radiotherapy provided by ExacTrac X-ray snap verification.

OBJECTIVE: To investigate the following hypotheses: (1) ExacTrac X-ray Snap Verification (ET-SV) is an alternative to CBCT for positioning patients with esophageal carcinoma (EC), (2) ET-SV can detect displacement in EC patients during radiotherapy (RT) and (3) EC patients can be feasibly monitored in quasi-real-time with ET-SV during RT. METHODS: Anthropomorphic phantoms and 13 patients were included in this study. CBCT and ET-SV were both implemented before treatment delivery to detect displacement, and their correction results were compared. For the patient tests, positional correction in 3 translational directions and the yaw direction were applied using the ET-SV correction results. The residual error was detected immediately using ET-SV. Finally, to acquire the intrafractional motion, ET-SV was implemented when the gantry was at 0°, 90°, 180° and 270°, respectively. RESULTS: In phantom tests, the maximum value of the difference in displacement between the CBCT and ET systems was 1.16 mm for translation and 0.31° for yaw. According to Bland-Altman analysis of the patient test results, 5% (5/98), 5% (5/98), 5% (5/98), and 4% (4/98) of points were beyond the upper and lower limits of agreement in the AP, SI, LR and yaw directions, respectively. The mean residual error was -0.482 mm, 1.215 mm, 1.0 mm, -0.487°, 0.105°, and 0.003° in the AP, SI, LR, pitch, roll and yaw directions, respectively. The intrafractional displacement ranged from -0.21 mm to 0 mm for translation and from -0.63° to 0.21° for rotation. The mean total translational error for intrafractional motion increased from 0.47 mm to 1.14 mm during the treatment. CONCLUSION: The accuracy of ET-SV for EC RT positional correction is comparable to that of CBCT. Thus, Quasi-real-time intrafractional monitoring can be used to detect EC patient displacement during radiotherapy.

Chinese expert recommendations on management of hepatocellular carcinoma during COVID-19 pandemic: a nationwide multicenter survey.

BACKGROUND: This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic. METHODS: A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic. RESULTS: 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the "face-to-face" visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC. DISCUSSION: During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery.

NEFL promotes invasion and migration of esophageal squamous carcinoma cells via the EGFR/AKT/S6 pathway.

To explore the expression, the roles and the underlying mechanism of neurofilament light chain (NEFL) in esophageal squamous cell carcinoma (ESCC), we firstly analyzed the NEFL mRNA and protein expression in ESCC and paired normal tissues by using Gene Expression Omnibus (GEO) database, and real-time quantitative reverse transcription PCR (qRT-PCR). The results showed that NEFL mRNA level was significantly upregulated in ESCC tissues compared with that of normal tissues. Western blot analysis revealed that NEFL protein level was also significantly upregulated in ESCC tissues. CCK8 and transwell assays were performed to analyze the effect of NEFL overexpression on the malignant phenotypes of ESCC cells, and the results showed that NEFL knockdown significantly impaired the ESCC cell invasion and migration in vitro. Xenograft assay in nude mice indicated that NEFL silencing suppressed tumor growth in vivo. At the molecular level, NEFL knockdown significantly upregulated E-cadherin and downregulated N-cadherin expression, suggesting that NEFL overexpression might influence the epithelial-mesenchymal transition (EMT) process. Furthermore, we found that NEFL knockdown significantly reduced the mRNA and protein expression of epidermal growth factor receptor (EGFR) and the phosphorylation levels of protein kinase B (PKB; also known as AKT) and ribosomal protein S6 (S6). Ectopic expression of EGFR after NEFL knockdown significantly restored the phosphorylation levels of AKT and S6 as well as the invasion and migration of ESCC cells. These data indicate that NEFL overexpression might promote the EMT process of ESCC cells via the EGFR/AKT/S6 pathway, ultimately enhancing the invasion and migration of ESCC cells.

Effectiveness of one-time endoscopic screening programme in prevention of upper gastrointestinal cancer in China: a multicentre population-based cohort study.

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.

Surveillance of premalignant gastric cardia lesions: A population-based prospective cohort study in China.

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.

International Trends in Esophageal Squamous Cell Carcinoma and Adenocarcinoma Incidence.

INTRODUCTION: We aimed to improve our understanding of the epidemiology of squamous cell carcinoma and adenocarcinoma of the esophagus. METHODS: We estimated average annual percent change and analyzed age-period-cohort trends on population-based cancer data. RESULTS: We found decreases in squamous cell carcinoma incidence in half of male populations (largest decrease in US black males [average annual percent change -7.6]) and increases in adenocarcinoma incidence in nearly a third of populations. Trends may be associated with a mix of birth cohort and period effects. DISCUSSION: More complete data and evidence are needed to conclude the reasons for the observed trends (see Visual Abstract, Supplementary Digital Content 4, http://links.lww.com/AJG/B823).

The association between anxiety and esophageal cancer: A nationwide population-based study.

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.

The associations of air pollution and socioeconomic factors with esophageal cancer in China based on a spatiotemporal analysis.

Rapid urbanization and industrialization in China have incurred serious air pollution and consequent health concerns. In this study, we examined the modifying effects of urbanization and socioeconomic factors on the association between PM2.5 and incidence of esophageal cancer (EC) in 2000-2015 using spatiotemporal techniques and a quasi-Poisson generalized linear model. The results showed a downward trend of EC and high-risk areas aggregated in North China and Huai River Basin. In addition, a stronger association between PM2.5 and incidence was observed in low urbanization group, and the association was stronger for females than males. When exposure time-windows were adjusted as 0, 5, 10, 15 years, the incidence risk increased by 2.48% (95% CI: 2.23%, 2.73%), 2.20% (95% CI: 1.91%, 2.49%), 2.18% (95% CI%: 1.92%, 2.43%), 1.87% (95% CI%:1.64, 2.10%) for males, respectively and 4.03% (95% CI: 3.63%, 4.43%), 2.20% (95% CI: 1.91%, 2.49%), 3.97% (95% CI: 3.54%, 4.41%), 3.06% (95% CI: 2.71%, 3.41%) for females, respectively. The findings indicated people in low urbanization group faced with a stronger EC risk caused by PM2.5, which contributes to a more comprehensive understanding of combating EC challenges related to PM2.5 pollution.