Selenium May Be Involved in Esophageal Squamous Cancer Prevention by Affecting GPx3 and FABP1 Expression: A Case-Control Study Based on Bioinformatic Analysis.

The role of selenium in the developmental process of esophageal cancer (EC) requires further investigation. To explore the relationship between selenium-related factors and EC through bioinformatic analysis, a case-control study was conducted to verify the results. Utilizing the GEPIA and TCGA databases, we delineated the differential expression of glutathione peroxidase 3 (GPx3) in EC and normal tissues, identified differentially expressed genes (DEGs), and a performed visualization analysis. Additionally, 100 pairs of dietary and plasma samples from esophageal precancerous lesions (EPLs) of esophageal squamous cancer (ESCC) cases and healthy controls from Huai'an district, Jiangsu, were screened. The levels of dietary selenium, plasma selenium, and related enzymes were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) or ELISA kits. The results showed lower GPx3 expression in tumor tissues compared to normal tissues. Further analysis revealed that DEGs were mainly involved in the fat digestion and absorption pathway, and the core protein fatty acid binding protein 1 (FABP1) was significantly upregulated and negatively correlated with GPx3 expression. Our case-control study found that selenium itself was not associated with EPLs risk. However, both the decreased concentration of GPx3 and the increase in FABP1 were positively correlated with the EPLs risk (p for trend = 0.035 and 0.046, respectively). The different expressions of GPx3 and FABP1 reflect the potential of selenium for preventing ESCC at the EPLs stage. GPx3 may affect myocardial infarction through FABP1, which remains to be further studied.

Influencing factors of knowledge proficiency of general practitioners in rural China for esophageal cancer prevention and treatment: a cross-sectional study.

BACKGROUND: This study aims to investigate the knowledge of rural general practitioners (GPs) in esophageal cancer (EC) prevention and treatment in China and analyze relevant influencing factors, so as to improve the ability of rural GPs in EC prevention and treatment. METHODS: This cross-sectional study was conducted from November 5, 2021, to November 20, 2021. A self-designed questionnaire was used to conduct an online survey. Multivariable logistic regression models were used to identify the influencing factors of knowledge proficiency of GPs in rural China for EC prevention and treatment. RESULTS: This study included 348 participants from 12 rural areas in Hebei Province. The mean accuracy rate on all question items was 42.3% ± 10.67%. Sex (OR = 2.870, 95% CI: 1.519-5.423), educational level (OR = 3.256, 95% CI: 1.135-9.339), and comprehension of clinical practice guidelines for EC (OR = 4.305, 95% CI: 2.023-9.161) were significant predictors for GPs' knowledge proficiency of EC prevention and treatment (P < 0.05). CONCLUSIONS: The study indicated that knowledge proficiency of rural GPs of EC prevention and control still awaits to be improved. Sex, educational level, and comprehension of clinical practice guidelines for EC were significant predictors for their proficiency.

Advances in Screening for Barrett Esophagus and Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC), the primary form of esophageal cancer in the United States, is a lethal cancer with exponentially increasing incidence. Screening for Barrett esophagus (BE), the only known precursor to EAC, followed by endoscopic surveillance to detect dysplasia and early-stage EAC and subsequent endoscopic treatment (to prevent progression of dysplasia to EAC and to treat early-stage EAC effectively) is recommended by several society guidelines. Sedated endoscopy (the primary current tool for BE screening) is both invasive and expensive, limiting its widespread use. In this review, we aim to provide a comprehensive review of recent innovations in the nonendoscopic detection of BE and EAC. These include swallowable cell sampling devices combined with protein and epigenetic biomarkers (which are now guideline endorsed as alternatives to sedated endoscopy), tethered capsule endomicroscopy, emerging peripheral blood-sampled molecular biomarkers, and exhaled volatile organic compounds. We also summarize progress and challenges in assessing BE and EAC risk, which is an important complementary component of the process for the clinical implementation of these innovative nonendoscopic tools, and propose a new paradigm for the strategy to reduce EAC incidence and mortality.

Antireflux Surgery Versus Antireflux Medication and Risk of Esophageal Adenocarcinoma in Patients With Barrett's Esophagus.

BACKGROUND & AIMS: Antireflux treatment is recommended to reduce esophageal adenocarcinoma in patients with Barrett's esophagus. Antireflux surgery (fundoplication) counteracts gastroesophageal reflux of all types of carcinogenic gastric content and reduces esophageal acid exposure to a greater extent than antireflux medication (eg, proton pump inhibitors). We examined the hypothesis that antireflux surgery prevents esophageal adenocarcinoma to a larger degree than antireflux medication in patients with Barrett's esophagus. METHODS: This multinational and population-based cohort study included all patients with a diagnosis of Barrett's esophagus in any of the national patient registries in Denmark (2012-2020), Finland (1987-1996 and 2010-2020), Norway (2008-2020), or Sweden (2006-2020). Patients who underwent antireflux surgery were compared with nonoperated patients using antireflux medication. The risk of esophageal adenocarcinoma was calculated using multivariable Cox regression, providing hazard ratios (HRs) and 95% CIs adjusted for age, sex, country, calendar year, and comorbidity. RESULTS: The cohort consisted of 33,939 patients with Barrett's esophagus. Of these, 542 (1.6%) had undergone antireflux surgery. During up to 32 years of follow-up, the overall HR was not decreased in patients having undergone antireflux surgery compared with nonoperated patients using antireflux medication, but rather increased (adjusted HR, 1.9; 95% CI, 1.1-3.5). In addition, HRs did not decrease with longer follow-up, but instead increased for each follow-up category, from 1.8 (95% CI, 0.6-5.0) within 1-4 years of follow-up to 4.4 (95% CI, 1.4-13.5) after 10-32 years of follow-up. CONCLUSIONS: Patients with Barrett's esophagus who undergo antireflux surgery do not seem to have a lower risk of esophageal adenocarcinoma than those using antireflux medication.

Revisiting Proton Pump Inhibitors as Chemoprophylaxis Against the Progression of Barrett's Esophagus.

PURPOSE OF REVIEW: Barrett's esophagus (BE) is associated with chronic gastroesophageal reflux disease and is a known precursor to esophageal adenocarcinoma. While endoscopic surveillance strategies and the role for endoscopic eradication therapy have been well established, there has been much interest in identifying chemopreventive agents to disrupt or halt the metaplasia-dysplasia-carcinoma sequence in patients with BE. RECENT FINDINGS: No pharmacological agent has held more hope in reducing the risk of neoplastic progression in BE than proton pump inhibitors (PPIs). However, data supporting PPIs for chemoprevention have largely been from observational cohort and case-control studies with mixed results. In this review, we revisit the literature and highlight the role of PPIs in patients with BE as it pertains to chemoprophylaxis against the progression of BE to dysplasia and esophageal adenocarcinoma.

Climate Change and the Esophagus: Speculations on Changing Disease Patterns as the World Warms.

PURPOSE OF REVIEW: Esophageal disorders, including gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), and esophageal cancer, may be affected by climate change. Our review describes the impact of climate change on risk factors associated with esophageal diseases and speculates how these climate-related factors impacted esophageal disorders and their management. RECENT FINDINGS: Climate change is responsible for extreme weather conditions (shifts in rainfall, floods, droughts, and forest fires) and global warming. These consequences affect basic human needs of water and food, causing changes in population dynamics and pose significant threats to digestive health, including common esophageal disorders like GERD, EoE, and esophageal cancers. The changing patterns of esophageal diseases with climate change are likely mediated through risk factors, including nutrition, pollutants, microplastics, and the microbiota-gut-brain axis. The healthcare process itself, including GI endoscopy practices commonly employed in diagnosing and therapeutics of esophageal diseases, may, in turn, contribute to climate change through plastic wastage and greenhouse gas emissions, thus creating the climate change lifecycle. Breaking the cycle would involve changes at the individual level, community level, and national policy level. Prevention is key, with individuals identifying and remediating risk factors and reducing carbon footprints. The ABC (Advocacy, Broadcast, and Collaborate) activities would help enhance awareness at the community level. Higher-level programs such as the Bracing Resilience Against Climate Effects (BRACE) would lead to broader and larger-scale adoption of public health adaptation strategies at the national level. The impact of climate change on esophageal disorders is likely real, mediated by several risk factors, and creates a climate change lifecycle that may only break if changes are made at individual, community, and national levels.

Statin use and its association with decreased risk of esophageal squamous cell carcinoma in betel nut chewers.

BACKGROUND: Betel nut chewing involves the chewing of areca nuts or betel quid (areca nuts wrapped in betel leaves), which is associated with an increased risk of esophageal squamous cell carcinoma (ESCC). Statins have anticancer properties. We investigated the association between statin use and ESCC risk in betel nut chewers. METHODS: The study included 105 387 betel nut chewers matched statin users and nonusers. Statin use was defined as the use of ≥28 cumulative defined daily doses (cDDDs) of statin. The primary outcome was incidence of ESCC. RESULTS: The incidence rate of ESCC was significantly lower in statin users than in nonusers (2.03 vs. 3.02 per 100 000 person-years). Statin users had a lower incidence rate ratio of 0.66 for ESCC (95% confidence interval [CI]: 0.43-0.85) relative to nonusers. After potential confounders were adjusted for, statin use was determined to be associated with a reduced risk of ESCC (adjusted hazard ratio [aHR], 0.68; 95% CI: 0.51-0.91). A dose-response relationship was observed between statin use and ESCC risk; the aHRs for statin use at 28-182 cDDDs, 183-488 cDDDs, 489-1043 cDDDs, and > 1043 cDDDs were 0.92, 0.89, 0.66, and 0.64, respectively. CONCLUSION: Statin use was revealed to be associated with a reduced risk of ESCC in betel nut chewers.

Exploring cell competition for the prevention and therapy of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is characterized by the development of cancer in the esophageal squamous epithelium through a step-by-step accumulation of genetic, epigenetic, and histopathological alterations. Recent studies have demonstrated that cancer-associated gene mutations exist in histologically normal or precancerous clones of the human esophageal epithelium. However, only a small proportion of such mutant clones will develop ESCC, and most ESCC patients develop only one cancer. This suggests that most of these mutant clones are kept in a histologically normal state by neighboring cells with higher competitive fitness. When some of the mutant cells evade cell competition, they become "super-competitors" and develop into clinical cancer. It is known that human ESCC is composed of a heterogeneous population of cancer cells that interact with and influence their environment and neighbors. During cancer therapy, these cancer cells not only respond to therapeutic agents but also compete with each other. Therefore, competition between ESCC cells within the same ESCC tumor is a constantly dynamic process. However, it remains challenging to fine-tune the competitive fitness of various clones for therapeutic benefits. In this review, we will explore the role of cell competition in carcinogenesis, cancer prevention, and therapy, using NRF2, NOTCH pathway, and TP53 as examples. We believe that cell competition is a research area with promising targets for clinical translation. Manipulating cell competition may help improve the prevention and therapy of ESCC.

The Protease Inhibitor Amprenavir Protects against Pepsin-Induced Esophageal Epithelial Barrier Disruption and Cancer-Associated Changes.

Gastroesophageal reflux disease (GERD) significantly impacts patient quality of life and is a major risk factor for the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Proton pump inhibitors (PPIs) are the standard-of-care for GERD and are among the most prescribed drugs in the world, but do not protect against nonacid components of reflux such as pepsin, or prevent reflux-associated carcinogenesis. We recently identified an HIV protease inhibitor amprenavir that inhibits pepsin and demonstrated the antireflux therapeutic potential of its prodrug fosamprenavir in a mouse model of laryngopharyngeal reflux. In this study, we assessed the capacity of amprenavir to protect against esophageal epithelial barrier disruption in vitro and related molecular events, E-cadherin cleavage, and matrix metalloproteinase induction, which are associated with GERD severity and esophageal cancer. Herein, weakly acidified pepsin (though not acid alone) caused cell dissociation accompanied by regulated intramembrane proteolysis of E-cadherin. Soluble E-cadherin responsive matrix metalloproteinases (MMPs) were transcriptionally upregulated 24 h post-treatment. Amprenavir, at serum concentrations achievable given the manufacturer-recommended dose of fosamprenavir, protected against pepsin-induced cell dissociation, E-cadherin cleavage, and MMP induction. These results support a potential therapeutic role for amprenavir in GERD recalcitrant to PPI therapy and for preventing GERD-associated neoplastic changes.

Missed opportunities to screen for Barrett's esophagus in the primary care setting of a large health system.

BACKGROUND AND AIMS: The rate of esophageal adenocarcinoma (EAC) is rising. This is partly due to the lack of identification of Barrett's esophagus (BE), the main risk factor for EAC. Identifying neoplastic BE can allow for endoscopic therapy to prevent EAC. Our aim was to determine how many patients eligible for screening are actually being screened for BE in the primary care setting of a large health system. METHODS: A digital search algorithm was constructed using the established gastroenterology guidelines and the Kunzmann model for screening for BE. The algorithm was then applied to the electronic medical record of all patients seen in the primary care setting of the health system. A manual review of charts of the identified patients was performed to confirm the high-risk status and determine if screening occurred. RESULTS: Of 936,371 primary care charts analyzed by the algorithm, 3535 patients (.4%) were determined to be high-risk for BE. Of these 3535 patients, only 1077 (30%) were screened for BE in clinical practice with endoscopy. The algorithm identified 2458 (70%) additional high-risk patients. Of the patients screened in clinical practice, 105 (10%) were found to have BE (10% with neoplasia). CONCLUSIONS: Numerous screening opportunities for BE are missed in the primary care setting of a large health system. Collaboration between gastroenterology and primary care services is needed to improve the screening rate.

Barrett's oesophagus and stage 1 oesophageal adenocarcinoma: monitoring and management

This guideline covers monitoring, treatment and follow-up for people aged 18 and over with Barrett's oesophagus and stage 1 oesophageal adenocarcinoma. It includes advice on endoscopic and non-endoscopic techniques. It aims to improve outcomes by ensuring the most effective investigations and treatments are used.

Quality of Online Information for Esophageal Cancer.

The Internet is a readily available source of information, and patients in North America frequently access it. Esophageal cancer is the 7th most common cancer worldwide, but there is a lack of studies examining esophageal cancer website quality. This current study looks to systematically analyze the quality of websites accessed by patients with esophageal cancer. A previously validated website evaluation tool was used to analyze the quality of online esophageal cancer resources for patients. The term "esophagus cancer" was used to retrieve hits from the search engine Google and the meta-search engines Dogpile and Yippy. A 100 website list was compiled using pre-specified inclusion and exclusion criteria. Websites were evaluated regarding administration, accountability, authorship, organization, readability, content, and accuracy. The term "esophagus cancer" returned over 500 websites from the search engines. Of the 100 websites included for analysis, 97% disclosed ownership, sponsorship, and advertising. Only 35% identified an author and even fewer (31%) gave the author's credentials. Only 31% declared updates to their information within the past 2 years. Readability scores revealed only 9%, and 12% of sites scored at an elementary level, according to the Flesch-Kincaid (FK) and SMOG scoring scales, respectively. The average FK and SMOG scores were 12.6 and 11.0, respectively. Detection was the most accurately described (70%). However, few websites provided accurate incidence/prevalence (28%), stage-specific prognosis (27%), or preventative information (17%). The quality of websites offering information on esophageal cancer is variable. While they overwhelmingly disclose website ownership interests, most do not identify authors, poorly describe important domains of esophageal cancer, and overall readability exceeds the commonly accepted level for non-healthcare professionals.

Esophageal cancer in China: Practice and research in the new era.

China, as the one of the largest developing countries in the world and with about one-fifth of the global population, is bearing an increasing burden on health from cancer. In the area of esophageal cancer (EC), China accounts for more than 50% of the global cases, with this disease being a particularly worse for those in disadvantaged populations. Along with China's socioeconomic condition, the epidemiology, diagnosis, therapeutics and research of EC have developed throughout the 21st century. In the current review, existing control measures for EC in China are outlined, including the incidence, mortality, screening, clinical diagnosis, multidisciplinary treatment and research landscape. EC in China are very different from those in some other parts of the world, especially in Western countries. Core measures that could contribute to the prevention of EC and improve clinical outcomes in patients of less developed countries and beyond are recommended. International cooperation among academia, government and industry is especially warranted in global EC control.

Gastroesophageal Reflux Disease Is Not a Great Screening Criterion: Time to Move on to Other Strategies for Controlling the Burden of Esophageal Adenocarcinoma.

ABSTRACT: Gastroesophageal reflux disease (GERD) is key in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma (EAC). Endoscopic screening of select individuals with GERD symptoms for Barrett's esophagus and EAC has been recommended, but the great majority of patients with EAC had never undergone prior screening, despite over a million esophagogastroduodenoscopies (EGDs) performed annually in the United States among individuals with GERD symptoms. This is likely due to a conflation among providers regarding diagnostic EGD in those with refractory symptoms and screening EGD. An alternative approach is needed that de-emphasizes GERD to avoid confusion and increase uptake of appropriate screening.

Health effects associated with vegetable consumption: a Burden of Proof study.

Previous research suggests a protective effect of vegetable consumption against chronic disease, but the quality of evidence underlying those findings remains uncertain. We applied a Bayesian meta-regression tool to estimate the mean risk function and quantify the quality of evidence for associations between vegetable consumption and ischemic heart disease (IHD), ischemic stroke, hemorrhagic stroke, type 2 diabetes and esophageal cancer. Increasing from no vegetable consumption to the theoretical minimum risk exposure level (306-372 g daily) was associated with a 23.2% decline (95% uncertainty interval, including between-study heterogeneity: 16.4-29.4) in ischemic stroke risk; a 22.9% (13.6-31.3) decline in IHD risk; a 15.9% (1.7-28.1) decline in hemorrhagic stroke risk; a 28.5% (-0.02-51.4) decline in esophageal cancer risk; and a 26.1% (-3.6-48.3) decline in type 2 diabetes risk. We found statistically significant protective effects of vegetable consumption for ischemic stroke (three stars), IHD (two stars), hemorrhagic stroke (two stars) and esophageal cancer (two stars). Including between-study heterogeneity, we did not detect a significant association with type 2 diabetes, corresponding to a one-star rating. Although current evidence supports increased efforts and policies to promote vegetable consumption, remaining uncertainties suggest the need for continued research.

Barrett Esophagus: Rapid Evidence Review.

Barrett esophagus is a premalignant change of the esophagus; however, malignant transformation to esophageal adenocarcinoma is rare in patients without dysplasia. Barrett esophagus is estimated to affect up to 5.6% of the U.S. population. Risk factors for Barrett esophagus include gastroesophageal reflux disease, obesity, age older than 50 years, male sex, tobacco use, and a family history of Barrett esophagus or esophageal adenocarcinoma. Patients who experience chronic gastroesophageal reflux symptoms plus additional risk factors should be considered for screening. Mucosal change consistent with Barrett esophagus is visualized during upper endoscopy; biopsy confirms the diagnosis and determines if dysplasia is present. Management of Barrett esophagus depends on the presence and severity of dysplasia; endoscopic treatment of dysplasia decreases the risk of malignant transformation. Surveillance after diagnosis is recommended to monitor for dysplasia and diagnose and treat esophageal adenocarcinoma at an earlier stage. Patients with Barrett esophagus should be offered proton pump inhibitor therapy to control reflux symptoms and possibly decrease the risk of developing esophageal adenocarcinoma. Statins, nonsteroidal anti-inflammatory drugs, and aspirin are associated with a decreased risk of esophageal adenocarcinoma in patients with Barrett esophagus; however, they should not generally be prescribed in the absence of another indication. Mortality benefits of screening and surveillance are uncertain.

Need for improvement in the evaluation of pre-malignant upper gastro-intestinal lesions in India: Results of a nationwide survey.

BACKGROUND AND AIM: Gastric and esophageal cancers are associated with high morbidity in India. In the absence of formal screening programs in India, it is essential that all elective esophago-gastro-duodenoscopies (EGDs), irrespective of indication, be also considered an opportunity to screen for premalignant lesions. With this premise, we tried to assess the adherence to best practices in the detection of premalignant upper gastro-intestinal lesions (PMUGIL) among endoscopists in India. We also evaluated the adequacy of training, availability of appropriate facilities, and differences between teaching and non-teaching centers. METHODS: We disbursed a survey among endoscopists working in India, through the membership database of the Society of Gastrointestinal Endoscopists of India, by email and instant messaging. The responses were collected and subsequently analyzed. RESULTS: We obtained a total of 422 eligible responses. The adherence to best practices assessed was lower than the set threshold in all except one parameter in both teaching centers and non-teaching centers. Only 58.5% of endoscopists had received training in the detection of PMUGIL. Appropriate image enhanced endoscopy (IEE) facilities were available to only 58.05% of surveyed endoscopists. CONCLUSIONS: Strategies to improve detection of PMUGIL should be directed at improving adherence to best practices, ensuring adequate training of endoscopists in the evaluation of PMUGIL and improving infrastructure.