Esophageal squamous cell carcinoma (ESCC) is the primary histological subtype of esophageal carcinoma, yet research on environmental exposure risks and associated metabolic alterations preceding ESCC is limited. In a nested case-control cohort of 396 adults (199 diagnosed with ESCC and 197 healthy controls (HC)), we combined exposomics and metabolomics to assess circulating chemical residues and early serum metabolic changes linked to ESCC risk. A cell experiment further evaluated the proliferative impact of 1H,1H,2H,2H-perfluorooctanesulfonic acid (6:2 FTS), identifying it as a risk factor for ESCC, primarily through lipid metabolism-related chronic inflammation. Significant metabolic disruptions were observed in ESCC cases, characterized by increased carnitines, phosphatidylcholines (PCs), and triglycerides (TGs) alongside reduced lysophosphatidylcholines (LPCs) and ether lysophosphatidylcholines (LPC-Os). An early-warning biomarker panel, including glutamic acid, methionine, choline, LPC-O 18:0, TG (14:0_18:2_20:5), and PC (18:0_20:4)/LPC 18:0, showed improved predictive capacity when combined with 6:2 FTS. Metabolome-exposome-wide association studies largely confirmed 6:2 FTS as a potential ESCC risk factor through lipid mediation. This study offers novel insights for ESCC prevention and early diagnosis through a combined biomarker panel integrating metabolic and environmental risk indicators.

Esophageal cancer (EC) is the sixth leading cause of cancer-related deaths in the United States, with a mere 20% survival rate in the first 5 years, making it a significant public health concern. Considering the lack of comprehensive evaluations of mortality trends, this study aims to provide an update on the mortality rates of esophageal cancer and its trends in the United States.

The mortality trends among adults with EC were analyzed using data from the CDC WONDER database. Crude and age-adjusted mortality rates (AAMRs) per 100,000 people were extracted. Annual percent changes (APCs) in AAMRs with 95% CI were obtained using joinpoint regression analysis across different demographic (sex, race/ethnicity, and age) and geographic (state, urban-rural, and regional) subgroups.

Between 1999 and 2020, 309,725 documented deaths were attributed to esophageal cancer. The overall AAMR decreased from 1999 to 2020 (6.69 to 5.68). Males had higher consistently higher AAMRs than females (10.96 vs. 2.24). NH White had the highest overall AAMR (6.88), followed by NH Black (6.46), NH American Indian (4.95), Hispanic or Latino (3.31), and NH Asian or Pacific Islander (2.57). AAMR also varied by region (overall AAMR: Midwest: 7.18; Northeast: 6.75; South: 6.07; West: 5.76), and nonmetropolitan areas had higher AAMR (non-core areas: 7.09; micropolitan areas: 7.19) than metropolitan areas (large central metropolitan areas: 5.75; large fringe areas: 6.33). The states in the upper 90th percentile of esophageal cancer-related AAMR were Vermont, District of Columbia, West Virginia, Ohio, New Hampshire, and Maine, and exhibited an approximately two-fold increase in AAMRs, compared with states falling in the lower 10th percentile.

Over the last 2 decades, there has been an overall decline in mortality related to EC in the United States. However, demographic and geographic discrepancies in EC-related mortality persist, necessitating additional exploration and development of specifically directed treatments.

The objective of this systematic review and dose‒response meta-analysis was to assess the associations between the dietary consumption of nitrate and nitrite and the risk of gastric and esophageal cancer.

MEDLINE, Scopus, Embase, Web of Science, Proquest, and Google Scholar were searched until April 1, 2024. Articles were selected by two independent researchers on the basis of the inclusion and exclusion criteria. Data regarding the study design, type of exposure and outcomes, intervals of intake of nitrate or nitrite in each layer, OR/RR/HR of the relationship for each layer of intake, total sample size, and number of cases of gastric or esophageal cancer were extracted. The certainty of the evidence was rated via the GRADE method. The pooled odds ratios, risk ratios, and dose‒response analyses were calculated via Stata version 17.0. The best-fit dose‒response model was assessed by the P value for linearity and nonlinearity. Study heterogeneity was assessed via the I2 and Q tests.

We found 2124 nonredundant studies, 234 of which were potentially relevant. Eighteen articles met the inclusion criteria and were included in the review. The results of the meta-analysis revealed a significant positive association between nitrite intake and gastric cancer in both case‒control studies (OR = 1.29, 95 % CI = 1.09-1.52, P value = 0.001, I2 = 1.91 %) and cohort studies (RR = 1.17, 95 % CI = 1.00-1.37, P value = 0.04, I2 = 0.00 %). In addition, case‒control studies revealed a nonsignificant inverse association between nitrate intake and gastric cancer incidence (OR = 0.71, 95 % CI = 0.50-1.01, P value = 0.06, I2 = 74.89 %), and cohort studies (RR = 0.89, 95 % CI = 0.73-1.09, P value = 0.27, I2 = 0.00 %). Case‒control studies also revealed no significant correlation between nitrite intake and esophageal cancer incidence (OR = 1.48, 95 % CI = 0.91 to 2.42, P value = 0.12, I2 = 0.001 %). Nitrites correlated linearly with gastric cancer (linearity P value = 0.001). The most appropriate fit models for the relationship between nitrate and gastric cancer were both piecewise linear and natural polynomial regression (quadratic) models (P values = 0.003 and 0.005, respectively). There was no significant publication bias.

According to this meta-analysis, high consumption of nitrites was associated with an increased risk of gastric cancer in case‒control and cohort studies with a linear regression model, and dietary nitrate intake was not associated with the risk of gastric cancer in either case‒control or cohort studies. These findings are inconclusive and require confirmation in future prospective studies with robust methodologies and adjustments for potential confounders.

This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC).

Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs).

A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403).

Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

The genomic characteristics of Peruvian patients with gastric adenocarcinoma from diverse socioeconomic backgrounds were examined in consideration of the possibility that patients from different socioeconomic backgrounds may be exposed to different risk factors. We conducted a prospective pilot study in two Peruvian cities (Lima and Ica). This study enrolled 15 patients from low socioeconomic status (LSES) and 15 patients from medium/high socioeconomic status (MHSES). The genomic profiling of gastric adenocarcinoma samples was done through the FoundationOne CDx platform. We compared the genomic characteristics and the need for targeted therapy and immunotherapy between LSES and MHSES. The genes with higher rates of alterations were TP53 (73.3% vs. 50.0%, P = 0.2635); CDH1 (26.7% vs. 28.6%, P = 1); CDKN2A (20.0% vs. 28.6%, P = 1); KRAS (33.3% vs. 7.1%, P = 0.1686); ARID1A (20.0% vs. 14.3%, P = 1); MLL2 (13.3% vs. 21.4%, P = 1) and SOX9 (33.3% vs. 0.0%, P = 0.0421) in LSES versus HMSES, respectively. There was no significant difference in tumor mutational burden (P = 0.377) or microsatellite status (P = 1). The LSES group had a higher need for targeted therapy or immunotherapy according to gene involvement and alterations. A significant genomic difference exists among patients with gastric adenocarcinoma of different socioeconomic status, which may result in a different need for targeted therapy and immunotherapy.

The genomic landscape of esophageal squamous cell cancer (ESCC), as well as its impact on the regulation of immune microenvironment, is not well understood. Thus, tumor samples from 92 patients were collected from two centers and subjected to targeted-gene sequencing. We identified frequently mutated genes, including TP53, KMT2C, KMT2D, LRP1B, and FAT1. The most frequent mutation sites were ALOX12B (c.1565C > T), SLX4 (c.2786C > T), LRIG1 (c.746A > G), and SPEN (c.6915_6917del) (6.5%). Pathway analysis revealed dysregulation of cell cycle regulation, epigenetic regulation, PI3K/AKT signaling, and NOTCH signaling. A 17-mutated gene-related risk model was constructed using random survival forest analysis and showed significant prognostic value in both our cohort and the validation cohort. Based on the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression (ESTIMATE) algorithm, the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm, and the MCPcounter algorithm, we found that the risk score calculated by the risk model was significantly correlated with stimulatory immune checkpoints (TNFSF4, ITGB2, CXCL10, CXCL9, and BTN3A1; p < 0.05). Additionally, it was significantly associated with markers that are important in predicting response to immunotherapy (CD274, IFNG, and TAMM2; p < 0.05). Furthermore, the results of immunofluorescence double staining showed that patients with high risk scores had a significantly higher level of M2 macrophage than those with low risk scores (p < 0.05). In conclusion, our study provides insights into the genomic landscape of ESCC and highlights the prognostic value of a genomic mutation signature associated with the immune microenvironment in southern Chinese patients with ESCC.

Individuals with metabolic syndrome exhibit simultaneously pro-thrombotic and pro-inflammatory conditions which more probably can lead to cardiovascular diseases progression, type 2 diabetes mellitus, and some types of cancer. The present scoping review is aimed at highlighting the association between cancer risk, inflammation, and metabolic syndrome.

A search strategy was performed, mixing keywords and MeSH terms, such as "Cancer Risk", "Inflammation", "Metabolic Syndrome", "Oncogenesis", and "Oxidative Stress", and matching them through Boolean operators. A total of 20 manuscripts were screened for the present study. Among the selected papers, we identified some associations with breast cancer, colorectal cancer, esophageal adenocarcinoma, hepatocellular carcinoma (HCC), and cancer in general.

Cancer and its related progression may also depend also on a latent chronic inflammatory condition associated with other concomitant conditions, including type 2 diabetes mellitus, metabolic syndrome, and obesity. Therefore, prevention may potentially help individuals to protect themselves from cancer.

Serum Cytokines Correlate with Pretreatment Body Mass Index-Adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery. Circulating cytokines have been linked to the development of esophageal squamous cell carcinoma (ESCC) and its associated malnutrition process. Nonetheless, given the varied disease stages and treatment modalities in previous studies, the clinical relevance of their findings is limited. We retrospectively studied 52 patients with stage III ESCC who underwent neoadjuvant chemoradiotherapy and curative-intent surgery. We investigated the association of clinicopathological features, pretreatment laboratory data, and pretreatment inflammatory status, as indicated by the levels of albumin, C-reactive protein, and 10 circulating cytokines, namely tumor necrosis factor-alpha (TNF-α), interferon-gamma, interleukin-1-beta (IL-1β), IL-4, IL-6, IL-8, IL-12, IL-13, IL-17A, and IL-23, with malnutrition, as shown by body mass index-adjusted body weight loss (BMI-BWL) grading, cancer progression. Half the patients showed severe malnutrition and high BMI-BWL grades (3 and 4). Multivariate analysis revealed an independent association between the levels of three cytokines (TNF-α, ≤ 5.8 pg/ml; IL-1β, > 0.4 pg/ml; IL-6, ≤ 12.4 pg/ml) and high BMI-BWL grades and between IL-4 levels > 22.5 pg/ml and cancer progression. All 10 cytokines were closely correlated with each other. In conclusion, TNF-α, IL-1β, and IL-6 were independent markers of malnutrition status and IL-4 was a prognostic factor for cancer progression in this patient population.

Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels.

The INTERSTROKE study is a case-control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined).

Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46-1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61-2.11) than ICH (OR 1.19 95% CI 1.00-1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24-4.10) and PAR (18.6%, 15.1-22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63-2.87) and undetermined cause (OR 1.97, 95% CI 1.55-2.50). Both filtered (OR 1.73, 95% CI 1.50-1.99) and non-filtered (OR 2.59, 95% CI 1.79-3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69-2.27), ischemic stroke (OR 1.89, 95% CI 1.59-2.24) and ICH (OR 2.00, 95% CI 1.60-2.50).

There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke.

The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Esophageal cancer (EC) is the eighth most common cancer worldwide. In view of biology and anatomical restrictions, multimodality treatment strategies have been developed for EC. However, the prognosis of patients with advanced EC remains especially poor. Immunotherapy, such as PD-1/PD-L1 and CTLA-4/B7 blockade, has emerged as a potent treatment for many types of cancer and has been approved in many countries. Based on the results of the ATTRACTION-3 trial, nivolumab, an anti-PD-1 monoclonal antibody, was approved by the US FDA for patients with platinum-resistant, unresectable, recurrent or metastatic esophageal squamous cell carcinoma. The CheckMate 648 trial demonstrated that the combination of nivolumab with platinum-based fluoropyrimidine chemotherapy and combination immunotherapy with nivolumab and ipilimumab, an anti-CTLA-4 monoclonal antibody, showed a survival benefit in patients with advanced esophageal squamous cell carcinoma compared with doublet chemotherapy. This review focuses on nivolumab-containing treatments for patients with advanced esophageal squamous cell carcinoma.

Background and Aim: Little is known about whether early menopause in Chinese ethnicity is associated with acute myocardial infarction (AMI). We aimed to determine whether self-reported early menopause (either surgical or natural menopause at an age <50 year) was associated with first AMI in Chinese women. Methods: The study population was from the INTERHEART China Study, part of the INTERHEART global study. INTERHEART global study was a standardized case-control study that was designed to evaluate the risk factors for first AMI among 52 countries. Data for demographic factors, education, income, and cardiovascular risk factors were obtained by structured questionnaires. A standard set of questions that inquired about menstrual history was included in the interview. Results: Of the 1,771 Chinese women, 1,563 (88.3%) reported either natural or surgical menopause. In univariate logistic regression model, women with early menopause had higher risk of AMI (odds ratio [OR]: 1.51; 95% confidence interval [CI]: 1.23-1.87). After controlling for age, birth control measures, type of menopause, and other traditional risk factors (including waist/hip ratio, lifestyle factors, history of hypertension and diabetes, psychosocial factors, and apolipoprotein B [ApoB]/A1 [ApoA1]), the risk for AMI remained (OR: 1.36; 95% CI: 1.03-1.79). The population attributable risk for AMI in women with early menopause at <50 years was 10.1% (95% CI: 4.0-20.0) compared with women who had menopause at ≥50 years. Conclusion: Early menopause is associated with increased risk of AMI in Chinese women, independent of other traditional coronary heart disease risk factors.

Background and aims: Experimental studies showed that carotenoids had anti-carcinogenic properties, but epidemiological studies on the association between dietary carotenoids and esophageal squamous cell carcinoma (ESCC) risk were limited, and the findings were inconsistent. This study aimed to investigate the roles of intake of dietary carotenoids in the development of ESCC among a rural Chinese population. Methods: A population-based case-control study was conducted in Southwest China. A total of 915 incident ESCC cases and 925 community-based controls were included. A validated food frequency questionnaire with 76-item was adopted to collect information about dietary consumption. Intake of dietary calories and each carotenoid was calculated according to the China food composition tables. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by a logistic regression model, with adjustments for age, gender, body mass index, family cancer history, cigarette smoking, alcohol drinking, education, marital status, prudent pattern score, and total calories. Results: In comparison to the highest with lowest intake quartiles, intake of total carotenes (OR: 0.70, 95% CI: 0.52-0.96, Ptrend: 0.024), α-carotene (OR: 0.62, 95% CI: 0.46-0.83, Ptrend: 0.014), β-carotene (OR: 0.63, 95% CI: 0.46-0.86, P-trend: 0.005), and the sum of lutein and zeaxanthin (OR: 0.41, 95% CI: 0.29-0.56, Ptrend<0.001) was significantly associated with a decreased risk of ESCC after adjustment for confounders. Conclusions: The results indicated that a higher intake of total carotene, α-carotene, β-carotene, and the sum of lutein and zeaxanthin was associated with a lower risk of ESCC.

Introduction: Poor oral hygiene is linked to high risks of many systemic diseases, including cancers. Oral dysbiosis is closely associated with poor oral hygiene, causing tooth loss, gingivitis, and periodontitis. We provide a summary of studies and discuss the risk factors for oesophageal squamous cell carcinoma (ESCC) from a microbial perspective in this review.Methods: A literature search of studies published before December 31, 2022 from PubMed, Web of Science, and The Cochrane Library was performed. The search strategies included the following keywords: (1) oral care, oral health, oral hygiene, dental health, dental hygiene, tooth loss, teeth loss, tooth absence, missing teeth, edentulism, tooth brushing, mouthwash, and tooth cleaning; (2) esophageal, esophagus, oesophagus, and oesophageal; (3) cancer, carcinoma, tumor, and neoplasm.Discussion: Poor oral health, indicated by infrequent tooth brushing, chronic periodontitis, and tooth loss, has been associated with an increased risk of squamous dysplasia and ESCC. Oral microbial diversity and composition are profoundly dysregulated during oesophageal tumorigenesis. Similar to the oral microbiota, the oesophageal microbiota varies distinctly in multiple bacterial taxa in ESCC and gastric cardia adenocarcinoma, both of which have high co-occurrence rates in the "Oesophageal Cancer Belt". In addition, the potential roles of oncogenic viruses in ESCC have also been discussed. We also briefly explore the potential mechanisms underlying the tumor-promoting role of dysregulated microbiota for the development of therapeutic targeting strategies.Conclusion: Poor oral health is an established risk indicator of ESCC. The dysbiosis of microbiota in upper gastrointestinal tract that highly resembles the oral microbial ecosystem but with distinct features at individual sites contributes to the development and progression of ESCC.

Esophageal cancer constitutes a global public health challenge. However, South Korean population-specific information on the association of lifestyle (smoking, alcohol consumption, and obesity status) with esophageal cancer risk is sparse. This nested case-control study analyzed the Korean national health screening cohort data (2002-2019) of 1114 patients with esophageal cancer and 4456 controls (1:4 propensity-score matched for sex, age, income, and residential region). Conditional and unconditional logistic regression analyses, after adjustment for multiple covariates, determined the effects of lifestyle factors on esophageal cancer risk. Smoking and alcohol consumption increased the esophageal cancer risk (adjusted odds ratio [95% confidence interval]: 1.37 [1.15-1.63] and 1.89 [1.60-2.23], respectively). Overweight (body mass index [BMI] ≥ 23 to <25 kg/m2), obese I (BMI ≥ 25 to <30 kg/m2), or obese II (BMI ≥ 30 kg/m2) categories had reduced odds of esophageal cancer (0.76 [0.62-0.92], 0.59 [0.48-0.72], and 0.47 [0.26-0.85], respectively). In the subgroup analyses, the association of incident esophageal cancer with smoking and alcohol consumption persisted, particularly in men or those aged ≥55 years, whereas higher BMI scores remained consistently associated with a reduced esophageal cancer likelihood across all age groups, in both sexes, and alcohol users or current smokers. Underweight current smokers exhibited a higher propensity for esophageal cancer. In conclusion, smoking and alcohol drinking may potentially increase the risk, whereas weight maintenance, with BMI ≥ 23 kg/m2, may potentially decrease the risk, for esophageal cancer in the South Korean population. Lifestyle modification in the specific subgroups may be a potential strategy for preventing esophageal cancer.

Given the poor prognosis of patients with lymph node metastasis, estimating the lymph node status in patients with early esophageal cancer is crucial. Indicators that could be used to predict lymph node metastasis in early esophageal cancer have been reported in many recent studies, but no recent studies have included a review of this subject.

To review indicators predicting lymph node metastasis in early esophageal squamous cell carcinoma (ESCC) and early esophageal adenocarcinoma (EAC).

We searched PubMed with "[early esophageal cancer (Title/Abstract)] and [lymph node (Title/Abstract)]" or "[early esophageal carcinoma (Title/Abstract)] and [lymph node (Title/Abstract)]" or "[superficial esophageal cancer (Title/Abstract)] and [lymph node (Title/Abstract)]." A total of 29 studies were eligible for analysis.

Preoperative imaging (size), serum markers (microRNA-218), postoperative pathology and immunohistochemical analysis (depth of invasion, tumor size, differentiation grade, lymphovascular invasion, neural invasion, expression of PIM-1 < 30%) were predictive factors for lymph node metastasis in both early ESCC and EAC. Serum markers (thymidine kinase 1 ≥ 3.38 pmol/L; cytokeratin 19 fragment antigen 21-1 > 3.30 ng/mL; stathmin-1) and postoperative pathology and immunohistochemical analysis (overexpression of cortactin, mixed-lineage leukaemia 2, and stanniocalcin-1) were predictive for lymph node metastasis in early ESCC. Transcription of CD69, myeloid differentiation protein 88 and toll-like receptor 4 and low expression of olfactomedin 4 were predictive of lymph node metastasis in early EAC. A total of 6 comprehensive models for early ESCC, including logistic regression model, nomogram, and artificial neural network (ANN), were reviewed. The areas under the receiver operating characteristic curve of these models reached 0.789-0.938, and the ANN performed best. As all these models relied on postoperative pathology, further models focusing on serum markers, imaging and immunohistochemical indicators are still needed.

Various factors were predictive of lymph node metastasis in early esophageal cancer, and present comprehensive models predicting lymph node metastasis in early ESCC mainly relied on postoperative pathology. Further studies focusing on serum markers, imaging and immunohistochemical indicators are still in need.

Previous studies have shown that ALDH2 and ADH1B genes may be associated with alcohol metabolism and the risk of esophageal squamous cell carcinoma (ESCC), with inconsistent results. This meta-analysis aimed at comprehensively assessing the associations between ALDH2 and ADH1B polymorphisms and the risk of ESCC to synthesize and clarify the evidence.

We calculated summary estimates of the associations between four genetic variants (rs671 and rs674 in ALDH2, and rs1229984 and rs1042026 in ADH1B) and the ESCC risk across 23 publications in the additive model and allelic model. Venice criteria, Bayesian false discovery probability (BFDP), and false-positive reporting probability (FPRP) were used to assess the strength of epidemiological evidence. Heterogeneity among studies was evaluated by using the Higgin's I2 statistic, and publication bias was assessed by using funnel plots and Begg's test. A Mendelian randomization (MR) analysis was performed to determine the causal association between alcohol intake and esophageal cancer risk. Data from the HaploReg v4.1 and PolyPhen-2 were analyzed for functional annotations.

Of the four genetic variants, rs671 of ALDH2 was associated with a significantly reduced risk of ESCC (OR: 0.60, 95% CI: 0.50-0.73), whereas rs1229984 of ADH1B was associated with a significantly increased risk (2.50, 95% CI: 1.70-3.69) in the additive model. In the allelic model, the variant rs1229984 of ADH1B also increased the risk of ESCC (OR: 1.50; 95% CI: 1.21-1.87). The result for the variant rs671 was considered as strong epidemiological evidence. Functional annotations identified that the four variants were related to the enhancer histone marks and motif changes. The other two variants were not associated with the ESCC risk (rs674 of ALDH2 OR: 1.22, 95% CI: 0.71-2.12; rs1042026 of ADH1B OR: 1.28, 95% CI: 0.52-3.14) in the additive model. The MR analysis did not find a causal effect of alcohol on the esophageal cancer risk.

The results showed that ADH1B rs1229984 was significantly associated with an increased the risk of ESCC.

Dietary effects on gastric and esophageal cancer by sex and smoking has rarely been investigated.

Individuals who had undergone national gastric cancer screening during 2008 and had no any cancer at baseline were enrolled and followed up to 2017. The gastric and esophageal cancer risk was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).

Among 3.645 million (44.1% men), 45,741 gastric cancers (67.7% men) and 3,550 esophageal cancers (89.5% men) developed during 9 years follow-up. In adjusted analysis, a frequent intake of fruit (≥ 7 servings per week) reduced the gastric cancer risk (aHR=0.91; 95% CI, 0.83-0.99) comparing to nearly no intake in women but slightly increased male gastric cancer risk (aHR=1.06; 95% CI, 1.00-1.13). A frequent intake of dietary fruit reduced the esophageal cancer risk only in men (aHR=0.75; 95% CI, 0.62-0.92). Frequent intake of red meat (3-4/week) slightly increased the gastric cancer risk only in men (aHR=1.04; 95% CI, 1.01-1.09). The favorable effect of fruit on the gastric and esophageal cancer risk was observed only in never smoker.

The effect of fruit and red meat intake on the gastric and esophageal cancer risk differed according to sex and smoking status.

The aim of this study was to describe the trends in incidence, mortality, and burden of esophageal cancer (EC) in Asia from 2010 through 2019 and compare with other global continental data.

We collected EC data from the 2019 Global Burden of Disease study from 2010 to 2019 in 49 countries and territories in Asia based on the sociodemographic index (SDI). For all locations, annual case data and age-standardized rates (ASRs) were extracted to investigate the EC incidence, prevalence, mortality, and disability-adjusted life-years (DALYs). The ASR relative difference (%) between years and the male/female (M/F) ratio were calculated. Data are reported in values and 95% uncertainty interval (UI).

In 2019, more than 70% of EC new cases, deaths, prevalence, and DALYs occurred in Asian countries. From 2010 to 2019, incidences, deaths, prevalence cases, and DALY number of EC increased over 1.10-, 1.07-, 1.14-, and 1.03-fold, in Asia. During this period, the age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), age-standardized prevalence rate (ASPR), and age-standardized DALYs rate (DALYs ASR) of EC decreased by 18, 21, 14, and 22%, respectively. The rate of decline in Asia is higher than in the world and other continents. In 2019, age-specific incidence, death, prevalence, and DALY cases of EC cancer peaked at 65-74, 70-74, 65-69, and 65-69 years, respectively. In 2019, the highest ASIR, ASDR, ASPR, and DALYs ASR of EC were observed in East Asian countries, while having the highest decreasing trend. In 2019, among high SDI Asian countries, Taiwan had the highest ASIR, ASPR, and DALYs ASR, and the United Arab Emirates had the highest ASDR. Among high-middle SDIs, Kazakhstan had the highest ASIR, ASPR, ASDR, and DALYs ASR; among middle SDIs, China had the highest ASIR, ASDR, and ASPR, and Viet Nam had the highest DALYs ASR; among low-middle SDIs, Mongolia had the highest ASIR, ASDR, ASPR, and DALY ASR of EC cancer. Among low SDI Asian countries, Pakistan had the highest ASIR and ASPR, and DALY ASR for EC cancer. For four indicators, in most countries, the ratio of men was higher than women, and in some countries, this ratio reached more than 10 times.

Although the rate of decline in incidence, death, prevalence and burden of EC in Asia was higher than in other areas in the last 10 years, more than 70% of these amounts occur in Asia. Therefore, it appears that adopting appropriate strategies in the field of identifying and controlling modifiable risk factors for EC, implementing screening programs, and timely diagnosis and treatment will help in reducing the burden of this disease in Asian countries.

Our study aimed to estimate the epidemiological trends of gastric cancer in the United States from 1992 to 2019. This population-based study used the US Surveillance, Epidemiology and End Results-12 database as a fundamental cohort to analyze gastric cancer incidence, incidence-based mortality (IBM), overall survival (OS) and cancer-specific survival (CSS) probabilities from 1992 to 2019. The Global Burden of Disease study (1990-2018) was used as a likely validation cohort. Age-period-cohort analyses were performed to explore the underlying causes of trend changes. We found that the incidence rate of gastric cancer decreased from 1992 to 2019. IBM also decreased significantly from 1997 to 2019. The 3-year OS and CSS of gastric cancer increased from 22.3% to 28.7% and 25.7% to 33.5%, respectively. However, the proportion of distant gastric cancer cases had unexpectedly increased rapidly from 33.1% in 1992 to 44.7% in 2019. Age-period-cohort modeling found that the incidence and IBM rates remained stable in the groups aged below 50 years, while that in all age groups older than 50 years showed a significant downward trend. High incidence and mortality risks were observed in the younger birth cohorts (birth year after 1990). To conclude, we observed a decline in incidence and mortality rates of gastric cancer in the United States in the past decades. We determined that progression of primary and tertiary preventive measures is the main reason for the reduction in the disease burden of gastric cancer. However, secondary preventive measures for gastric cancer still need to be strengthened.

Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in-person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66-1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post-hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27-0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08-0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.

A decrease in cancer mortality has been reported in the USA, possibly due to decreased incidence, downstaging and improved survival. The aim of the present study is to estimate the contribution of these factors on the trend in cancer mortality.

Data on incidence, mortality, stage at diagnosis, and overall and stage-specific survival for six common digestive and respiratory cancers (esophagus, stomach, colorectal, liver, pancreas and lung) during 2009-2013 in the USA from the surveillance, epidemiology and end results (SEER) program, was analyzed using generalized linear models separately among men and women.

Our study showed a decrease in mortality for esophageal (-0.09/100 000/year and -0.03/100 000/year), stomach (-0.11/100 000/year and -0.05/100 000/year), colorectal (-0.45/100 000/year and -0.29/100 000/year) and lung cancer (-1.89/100 000/year in men and -0.78/100 000/year in women) in men and women, respectively: for all of them, except lung cancer in women, there was a decrease in the incidence of comparable or greater magnitude; stage distribution and survival also contributed to the decrease in mortality for lung and colorectal cancer. Mortality from pancreatic cancer was stable: an increase in incidence was counterbalanced by an improvement in survival. Mortality from liver cancer increased, driven by an increase in mortality that was not offset by favorable trends in stage distribution and survival.

Trends in mortality were primarily affected by changes in incidence; an increase in the proportion of local stage at diagnosis and improved survival, although evident for some cancers, played a lesser role in mortality trends.

To identify the main risk factors for metachronous metastatic nasopharyngeal carcinoma (NPC) in different periods after radiotherapy and estimate the weight of various factors in the early or late metachronous metastasis (EMM/LMM) groups.

This retrospective registry consists of 4434 patients with newly diagnosed NPC. Cox regression analysis was used to assess the independent significance of various risk factors. The Interactive Risk Attributable Program (IRAP) was used to calculate the attributable risks (ARs) for metastatic patients during different periods.

Among 514 metastatic patients, 346 (67.32%) patients diagnosed with metastasis within 2 years after treatment were classified into the EMM group, while other 168 patients were classified into the LMM group. The ARs of T-stage, N-stage, pre-Epstein-Barr virus (EBV) DNA, post-EBV DNA, age, sex, pre-neutrophil-to-lymphocyte ratio, pre-platelet-to-lymphocyte ratio, pre-hemoglobin (HB), and post-HB were 20.19, 67.25, 2.81, 14.28, 18.50, - 11.17%, 14.54, 9.60, 3.74% and - 9.79%, respectively, in the EMM group. In the LMM group, the corresponding ARs were 3.68, 49.11, - 18.04%, 2.19, 6.11, 0.36, 4.62, 19.77, 9.57 and 7.76%, respectively. After multivariable adjustment, the total AR for tumor-related factors was 78.19%, and that for patient-related factors was 26.07% in the EMM group. In the LMM group, the total AR of tumor-related factors was 43.85%, while the weights of patient-related factors was 39.97%. In addition, except for these identified tumor- and patient-related factors, other unevaluated factors played a more important role in patients with late metastasis, with the weight increasing by 15.77%, from 17.76% in the EMM group to 33.53% in the LMM group.

Most metachronous metastatic NPC cases occurred in the first 2 years after treatment. Early metastasis was mainly affected by tumor-related factors, which accounted for a declining percentage in the LMM group.

Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence, survival, and risk factors. Although the genomic characteristics of ESCC have been extensively characterized, the genomic differences between different geographic regions remain unclear.

In this study, we sequenced 111 patients with ESCC from northern (NC) and southern (SC) China, combined their data with those of 1081 cases from previous reports, and performed a comparative analysis among different regions. In total, 644 ESCC cases were collected from six geographic regions (NC, SC, Xinjiang, China [XJC], Japan [JP], Vietnam [VN], and Europe & America [EA]) as the discovery cohort. Validation cohort 1 included 437 patients with ESCC from the NC region. Validation cohort 2 included 54 and 57 patients from the NC and SC regions, respectively.

Patients with ESCC in different regions had different genomic characteristics, including DNA signatures, tumor mutation burdens, significantly mutated genes (SMGs), altered signaling pathways, and genes associated with clinical features. Based on both the DNA mutation signature and the mutation profile of the most common genes, the NC and SC groups were clustered close together, followed by the JP, XJC, EA, and VN groups. Compared to patients with ESCC from SC, SMGs, including KMT2D, FAT1, and NOTCH1 were more frequently identified in patients with ESCC from NC. Furthermore, some genes (TDG and DNAH8) correlated with overall survival in completely opposite ways in patients with ESCC from different geographical regions.

Our study provides insights into genomic differences in ESCC among different regions. These differences may be related to differences in environmental carcinogens, incidence, and survival.

Recently, epidemiological evidence of high-risk human papillomavirus (hrHPV) and its association with the increasing risk of esophageal cancer (EC) have been described. However, the involvement of such a virus in the pathogenesis of EC is still inconclusive in the literature. Therefore, our objective was to clarify the epidemiology of HPV infections in primarily diagnosed EC cases and validate this correlation with hospital-based control patients using a retrospective study with a case-control model. Here, we reported that the overall prevalence of HPV DNA was statistically associated with an increased risk of EC (OR, 3.3; 95% CI, 2.5-4.3). Interestingly, a history of gastroesophageal reflux disease (GERD) was constituted and significantly associated with HPV prevalence (adjusted OR, 4.6; 95% CI, 2.2-9.5). Furthermore, our meta-analysis in public databases also indicated that the combined OR and 95% CI between HPV infection and EC risk were 3.31 and 2.53-4.34, respectively, with significant heterogeneity (I₂ = 78%). Variations in the geographic study, tissue type, and detection method remain potential predictors of heterogeneity. In addition, publication bias and sensitivity analysis were not observed, and the results exhibited stable outcomes. Collectively, we specify the recent epidemiological evidence in a validation of the distributed HPV, which might be statistically associated with an increased risk of EC. However, additional high-quality studies with larger sample sizes are needed to further verify the link between HPV and EC.

White light imaging (WLI) is the most common endoscopic technique used for screening of gastrointestinal diseases. However, despite the advent of a new processor that offers sufficient clear illumination and other advanced developments in endoscopic instrumentation, WLI alone is inadequate for detecting all gastrointestinal diseases with abnormalities in mucosal discoloration and morphological changes to the mucosal surface. The recent development of image-enhanced endoscopy (IEE) has dramatically improved the detection of gastrointestinal diseases. Texture and colour enhancement imaging (TXI) is a new type of IEE that enhances brightness, surface irregularities, such as elevations or depressions, and subtle colour changes. TXI with two modes, namely modes 1 and 2, can selectively enhance brightness in dark areas of an endoscopic image and subtle tissue differences such as slight morphological or colour changes while simultaneously preventing over-enhancement. Several clinical studies have investigated the efficacy of TXI for detecting and visualizing gastrointestinal diseases, including oesophageal squamous cell carcinoma (ESCC), Barret's epithelium, gastric cancer, gastric mucosal atrophy and intestinal metaplasia. Although TXI is often more useful for detecting and visualizing gastrointestinal diseases than WLI, it remains unclear whether TXI outperforms other IEEs, such as narrow-band imaging (NBI), in similar functions, and whether the performance of TXI modes 1 and 2 are comparable. Therefore, large-scale prospective studies are needed to compare the efficacy of TXI to WLI and other IEEs for endoscopic evaluation of patients undergoing screening endoscopy. Here, we review the characteristics and efficacy of TXI for the detection and visualization of gastrointestinal diseases.Key MessagesTXI mode 1 can improve the visibility of gastrointestinal diseases and qualitative diagnosis, especially for diseases associated with colour changes.The enhancement of texture and brightness with TXI mode 2 enables the detection of diseases, and is ideal for use in the first screening of gastrointestinal tract.

The Herat province of Afghanistan is located on the Asian Esophageal Cancer Belt (AECB), a wide area in Central and Eastern Asia where very high rates of esophageal cancer (EC) have been observed. Several risk factors have been reported in the AECB Region by previous studies. Considering lack of information in Afghanistan on this issue, a study was conducted to determine the major risk factors related to EC in order to guide protective measures.

A population-based case-control study was performed from July 2015 to August 2016 among 657 EC patients in the Herat Province and 180 histopathological confirmed cases and 189 controls were interviewed. A structured questionnaire was used and face-to-face interviews were conducted.

Low body mass index (BMI), low socio-economic status, family history of EC, consumption of dark tea, very hot beverage and qulurtoroosh were found to be statistically significant for EC and esophageal squamous cell carcinoma (ESCC) in univariate analyses. According to multivariate analyses, sex (OR=2.268; 95% CI=1.238-4.153), very hot beverages (OR=2.253; 95% CI=1.271- 3.996), qulurtoroosh (OR=5.679; 95% CI=1.787-18.815), dark tea (OR=2.757; 95% CI=1.531-4.967), high previous BMI (OR=0.215; 95% CI=0.117-0.431) and low socio-economic status (OR=1.783; 95% CI=1.007-3.177) were associated with ESCC. Being male was found to increase the risk of ESCC with OR=2.268 (95% CI=1.238-4.153).

Consuming very hot beverages dark tea and a local food, qulurtoroosh, were found as important risk factors for EC. Our findings warrant further studies and necessitate the implementation of protective measures for EC which is one of the leading cancers in the region.

Esophageal squamous cell carcinoma (ESCC) has a poor prognosis; therefore, early detection is essential. In Japan, more than 90% of esophageal cancers are ESCC. Endoscopy is effective to detect ESCC in the early stage, but there is a limited number of reports examining its efficacy and effectiveness.

This study aimed to evaluate the efficacy of screening endoscopy for detecting ESCC.

This retrospective study analyzed the prevalence of ESCC, annual transition of prevalence, and the stage of each ESCC among 128,520 medical check-up patients who underwent esophagogastroduodenoscopy from April 2015 to March 2020 at Yamanashi Koseiren Health Care Center. Furthermore, a case-control study utilized the multivariate logistic regression analysis was performed to assess the risk factor of ESCC.

Among a total of 128,520 subjects, 42 ESCC patients were detected, with 95.2% being diagnosed at early stages. Annual prevalence in males was 0.015% (2/13,122) in 2015, 0.044% (6/13,562) in 2016, 0.044% (6/13,676) in 2017, 0.074% (10/13,488) in 2018%, and 0.11% (16/14,386) in 2019. ESCC prevalence has been increasing each year. A significant increase was observed between 2015 and 2018 (p = 0.039). ESCC prevalence was 0.102% (25/24,272) when focusing on males aged over 50 years with a history of smoking and drinking. Regarding the case-control study, the multivariate logistic regression analysis revealed smoking (p = 0.044), mean corpuscular volume (MCV) (p = 0.0018), and severe gastric atrophy (p = 0.048) as positively correlated with ESCC.

In conclusion, ESCC has been increasing in our center from 2015 to 2019, and the prevalence has been approaching that of gastric cancer in 2019 in male subjects. ESCC can be detected efficiently by targeting males with high MCV who have a history of drinking and smoking.

Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability.

Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression.

Although the standard approach did not identify significant signals, the eQTL set-based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641, and HSP90AA1).

This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set-based genetic association approach.

This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set-based genetic association approach as an alternative method for TWAS analysis.