Interventional gastroenterology in oncology.

Cancer is one of the foremost health problems worldwide and is among the leading causes of death in the United States. Gastrointestinal tract cancers account for almost one third of the cancer-related mortality globally, making it one of the deadliest groups of cancers. Early diagnosis and prompt management are key to preventing cancer-related morbidity and mortality. With advancements in technology and endoscopic techniques, endoscopy has become the core in diagnosis and management of gastrointestinal tract cancers. In this extensive review, the authors discuss the role endoscopy plays in early detection, diagnosis, and management of esophageal, gastric, colorectal, pancreatic, ampullary, biliary tract, and small intestinal cancers.

QSOX1 facilitates dormant esophageal cancer stem cells to evade immune elimination via PD-L1 upregulation and CD8 T cell exclusion.

Dormant cancer stem cells (DCSCs) exhibit characteristics of chemotherapy resistance and immune escape, and they are a crucial source of tumor recurrence and metastasis. However, the underlying mechanisms remain unrevealed. We demonstrate that enriched Gzmk+ CD8+ T cells within the niche of esophageal DCSCs restrict the outgrowth of tumor mass. Nonetheless, DCSCs can escape immune elimination by enhancing PD-L1 signaling, thereby maintaining immune equilibrium. Quiescent fibroblast-derived quiescin sulfhydryl oxidase 1 (QSOX1) promotes the expression of PD-L1 and its own expression in DCSCs by elevating the level of reactive oxygen species. Additionally, high QSOX1 in the dormant tumor niche contributes to the exclusion of CD8+ T cells. Conversely, blocking QSOX1 with Ebselen in combination with anti-PD-1 and chemotherapy can effectively eradicate residual DCSCs by reducing PD-L1 expression and promoting CD8+ T cell infiltration. Clinically, high expression of QSOX1 predicts a poor response to anti-PD-1 treatment in patients with esophageal cancer. Thus, our findings reveal a mechanism whereby QSOX1 promotes PD-L1 upregulation and T cell exclusion, facilitating the immune escape of DCSCs, and QSOX1 inhibition, combined with immunotherapy and chemotherapy, represents a promising therapeutic approach for eliminating DCSCs and preventing recurrence.

Zinc treatment reverses and anti-Zn-regulated miRs suppress esophageal carcinomas in vivo.

Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% decrease in ESCC incidence vs. Zn-untreated controls. Zn treatment eliminated ESCCs by affecting a spectrum of biological processes that included downregulation of expression of the two miRs and miR-31-controlled inflammatory pathway, stimulation of miR-21-PDCD4 axis apoptosis, and reversal of the ESCC metabolome: with decrease in putrescine, increase in glucose, accompanied by downregulation of metabolite enzymes ODC and HK2. Thus, Zn treatment or miR-31/21 silencing are effective therapeutic strategies for ESCC in this rodent model and should be examined in the human counterpart exhibiting the same biological processes.

Dual roles of HSP70 chaperone HSPA1 in quality control of nascent and newly synthesized proteins.

Exposure to heat stress triggers a well-defined acute response marked by HSF1-dependent transcriptional upregulation of heat shock proteins. Cells allowed to recover acquire thermotolerance, but this adaptation is poorly understood. By quantitative proteomics, we discovered selective upregulation of HSP70-family chaperone HSPA1 and its co-factors, HSPH1 and DNAJB1, in MCF7 breast cancer cells acquiring thermotolerance. HSPA1 was found to have dual function during heat stress response: (i) During acute stress, it promotes the recruitment of the 26S proteasome to translating ribosomes, thus poising cells for rapid protein degradation and resumption of protein synthesis upon recovery; (ii) during thermotolerance, HSPA1 together with HSPH1 maintains ubiquitylated nascent/newly synthesized proteins in a soluble state required for their efficient proteasomal clearance. Consistently, deletion of HSPH1 impedes thermotolerance and esophageal tumor growth in mice, thus providing a potential explanation for the poor prognosis of digestive tract cancers with high HSPH1 and nominating HSPH1 as a cancer drug target. We propose dual roles of HSPA1 either alone or in complex with HSPH1 and DNAJB1 in promoting quality control of nascent/newly synthesized proteins and cellular thermotolerance.

Risk of Esophageal Adenocarcinoma After Helicobacter pylori Eradication Treatment in a Population-Based Multinational Cohort Study.

BACKGROUND & AIMS: Helicobacter pylori infection is associated with a decreased risk of esophageal adenocarcinoma, and the decreasing prevalence of such infection might contribute to the increasing incidence of this tumor. We examined the hypothesis that eradication treatment of H pylori increases the risk of esophageal adenocarcinoma. METHODS: This population-based multinational cohort, entitled "Nordic Helicobacter Pylori Eradication Project (NordHePEP)," included all adults (≥18 years) receiving H pylori eradication treatment from 1995-2018 in any of the 5 Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) with follow-up throughout 2019. Data came from national registers. We calculated standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) by dividing the cancer incidence in the exposed cohort by that of the entire Nordic background populations of the corresponding age, sex, calendar period, and country. Analyses were stratified by factors associated with esophageal adenocarcinoma (ie, education, comorbidity, gastroesophageal reflux, and certain medications). RESULTS: Among 661,987 participants who contributed 5,495,552 person-years after eradication treatment (median follow-up, 7.8 years; range, 1-24 years), 550 cases of esophageal adenocarcinoma developed. The overall SIR of esophageal adenocarcinoma was not increased (SIR = 0.89; 95% CI, 0.82-0.97). The SIR did not increase over time after eradication treatment, but rather decreased and was 0.73 (95% CI, 0.61-0.86) at 11-24 years after treatment. There were no major differences in the stratified analyses. The overall SIR of esophageal squamous cell carcinoma, calculated for comparison, showed no association (SIR = 0.99; 95% CI, 0.89-1.11). CONCLUSIONS: This absence on an increased risk of esophageal adenocarcinoma after eradication treatment of H pylori suggests eradication is safe from a cancer perspective.

Incidence and Prediction of Unrelated Mortality After Successful Endoscopic Eradication Therapy for Barrett's Neoplasia.

BACKGROUND & AIMS: Follow-up (FU) strategies after endoscopic eradication therapy (EET) for Barrett's neoplasia do not consider the risk of mortality from causes other than esophageal adenocarcinoma (EAC). We aimed to evaluate this risk during long-term FU, and to assess whether the Charlson Comorbidity Index (CCI) can predict mortality. METHODS: We included all patients with successful EET from the nationwide Barrett registry in the Netherlands. Data were merged with National Statistics for accurate mortality data. We evaluated annual mortality rates (AMRs, per 1000 person-years) and standardized mortality ratio for other-cause mortality. Performance of the CCI was evaluated by discrimination and calibration. RESULTS: We included 1154 patients with a mean age of 64 years (±9). During median 59 months (p25-p75 37-91; total 6375 person-years), 154 patients (13%) died from other causes than EAC (AMR, 24.1; 95% CI, 20.5-28.2), most commonly non-EAC cancers (n = 58), cardiovascular (n = 31), or pulmonary diseases (n = 26). Four patients died from recurrent EAC (AMR, 0.5; 95% CI, 0.1-1.4). Compared with the general Dutch population, mortality was significantly increased for patients in the lowest 3 age quartiles (ie, age <71 years). Validation of CCI in our population showed good discrimination (Concordance statistic, 0.78; 95% CI, 0.72-0.84) and fair calibration. CONCLUSION: The other-cause mortality risk after successful EET was more than 40 times higher (48; 95% CI, 15-99) than the risk of EAC-related mortality. Our findings reveal that younger post-EET patients exhibit a significantly reduced life expectancy when compared with the general population. Furthermore, they emphasize the strong predictive ability of CCI for long-term mortality after EET. This straightforward scoring system can inform decisions regarding personalized FU, including appropriate cessation timing. (NL7039).

A HIGH-RESOLUTION MICROENDOSCOPE IMPROVES ESOPHAGEAL CANCER SCREENING AND SURVEILLANCE: IMPLICATIONS FOR UNDERSERVED GLOBAL SETTINGS BASED ON AN INTERNATIONAL, RANDOMIZED CONTROLLED TRIAL.

BACKGROUND AND AIMS: Lugol's chromoendoscopy (LCE)-based detection of esophageal squamous cell neoplasia (ESCN) is limited by low specificity. High-resolution microendoscopy (HRME) was shown to improve specificity and reduce unnecessary biopsies when used by academic endoscopists. In this international, randomized controlled trial, we determined the clinical impact, efficiency, and performance of HRME in true global health contexts with a range of providers. METHODS: Subjects undergoing screening or surveillance for ESCN by expert and novice endoscopists were enrolled in China and the U.S. from diverse clinical settings. Subjects were randomized to LCE (standard-of-care) or LCE+HRME (experimental). Primary outcomes were efficiency and clinical impact of LCE vs. LCE+HRME, using gold-standard, consensus pathology. RESULTS: Among 916 consented subjects, 859 (93.8%) were recruited in China and 36 (3.9%) in the U.S.; 21 (2.3%) were excluded due to incomplete procedure or data. In the screening arm, 217 subjects were randomized to LCE, 204 to LCE+HRME; in the surveillance arm, 236 were randomized to LCE, 238 to LCE+HRME. HRME increased efficiency in screening: diagnostic yield (neoplastic/total biopsies) improved from 20.0% (95% confidence interval [CI] 12.7-29.2%) to 51.7% (95% CI 32.5-70.6%) with 65.2% (95% CI 54.6-74.9%) of biopsies potentially saved and 59.7% (95% CI 47.5-71.1%) of subjects potentially spared any biopsy. Six subjects (0.7%) had neoplasia missed by the endoscopist on HRME (false negatives); of these, 3 were moderate or high-grade dysplasia missed by novices. CONCLUSION: A low-cost microendoscope improves the efficiency and clinical impact of ESCN screening and surveillance when combined with LCE. HRME may spare unnecessary biopsies leading to cost savings in underserved global settings where the disease is prevalent. CLINICALTRIALS: gov, Number NCT02029937.

The causal associations of circulating lipids with Barrett's Esophagus and Esophageal Cancer: a bi-directional, two sample mendelian randomization analysis.

OBJECTIVE: The causal associations of circulating lipids with Barrett's Esophagus (BE) and Esophageal Cancer (EC) has been a topic of debate. This study sought to elucidate the causality between circulating lipids and the risk of BE and EC. METHODS: We conducted two-sample Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) of circulating lipids (n = 94,595 - 431,167 individuals), BE (218,792 individuals), and EC (190,190 individuals) obtained from the publicly available IEU OpenGWAS database. The robustness and reliability of the results were ensured by employing inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO methods. The presence of horizontal pleiotropy, heterogeneities, and stability of instrumental variables were assessed through MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis. Additionally, bidirectional MR and multivariable MR (MVMR) were performed to explore reverse causality and adjust for known confounders, respectively. RESULTS: None of the testing methods revealed statistically significant horizontal pleiotropy, directional pleiotropy, or heterogeneity. Univariate MR analyses using IVW indicated a robust causal relationship between increased triglycerides and BE (odds ratio [OR] = 1.79, p-value = 0.009), while no significant association with EC was observed. Inverse MR analysis indicated no evidence of reverse causality in the aforementioned outcomes. In MVMR analyses, elevated triglycerides (TRG) were significantly and positively associated with BE risk (OR = 1.79, p-value = 0.041). CONCLUSION: This MR study suggested that genetically increased triglycerides were closely related to an elevated risk of BE, potentially serving as a biomarker for the diagnosis of BE in the future.

Tumor-derived exosomal hyaluronidase 1 induced M2 macrophage polarization and promoted esophageal cancer progression.

The communication between tumor-derived exosomes and macrophages plays an important role in facilitating the progression of tumors. However, the regulatory mechanisms by which exosomes regulate tumor progression in esophageal squamous cell carcinoma (ESCC) have not been fully elucidated. We constructed a coculture system containing an ESCC cell line and macrophages using a Transwell chamber. We isolated exosomes from the conditioned medium of cancer cells, and characterized them with transmission electron microscopy and western blotting and used then to treat macrophages. We used co-immunoprecipitation to evaluate the interaction between hyaluronidase 1 (HYAL1) and Aurora B kinase (AURKB). We evaluated HYAL1 and AURKB expression in tissues and cells with quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and western blotting. We used RT-qPCR, enzyme-linked immunosorbent assay (ELISA) and flow cytometry to detect macrophage polarization. We assessed cell viability, invasion and migration with the cell counting kit-8 (CCK-8), Transwell and wound healing assays. HYAL1 was highly expressed in ESCC tissues and cells and cancer cell-derived exosomes, and exosomes can be delivered to macrophages through the cancer cell-derived exosomes. The exosomes extracted from HYAL1-overexpressed ESCC cells suppressed M1 macrophage polarization and induced M2 macrophage polarization, thereby promoting ESCC cell viability, invasion and migration. HYAL1 silencing in ESCC cells produced the opposite effects on macrophage polarization and cancer cell functions. We found that HYAL1 interacted with AURKB and further activated the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in macrophages. In conclusion, ESCC-derived exosomes containing HYAL1 facilitate M2 macrophage polarization by targeting AURKB to active the PI3K/AKT signaling pathway, which in turn promotes ESCC progression.

FAM83D promotes the progression of 4NQO-induced esophageal carcinoma via inhibiting FBWX7.

The present study aimed to explore the expression and regulatory role of FAM83D in the different developmental stages of esophageal squamous cell carcinoma (ESCC) to determine the effect of FAM83D on the proliferation, migration, and invasion of ESCC cells and to elucidate its underlying molecular mechanism. Immunohistochemistry (IHC) analysis revealed that the expression of FAM83D was obviously elevated in ESCC tissues compared to adjacent normal tissues. Furthermore, the FAM83D levels was positively correlated with tumor size, TNM stage, T stage, and N stage, while it was negatively correlated with FBXW7 expression, Karnofsky Performance Status (KPS) score, and survival rate. Subsequently, ESCC cell lines with low FAM83D expression were constructed using RNA interference technology to investigate the impact of FAM83D on the biological behavior of ESCC cells. Silencing of FAM83D inhibited the proliferation and migration of ESCC cells but promoted apoptosis. Furthermore, a reduction in FAM83D expression may also induce cell cycle arrest at the G0/G1 phase and regulate the expression of proteins related to epithelial-mesenchymal transition (EMT), the cell cycle, and apoptosis. Further research indicated that silencing FAM83D led to the upregulation of FBXW7 expression. These results suggested that FAM83D may exert its effects on ESCC by downregulating FBXW7. Additionally, using a 4NQO solution in the drinking water to establish an ESCC mouse model, IHC analysis revealed that FAM83D expression levels were positively correlated with the pathological grade of esophageal lesions in the mice and negatively correlated with the expression levels of FBXW7 and E-cadherin. The above results demonstrated that FAM83D may facilitate the progression of ESCC by negatively regulating FBXW7 expression and that FAM83D could represent a promising therapeutic target for ESCC.

Sulconazole Induces PANoptosis by Triggering Oxidative Stress and Inhibiting Glycolysis to Increase Radiosensitivity in Esophageal Cancer.

Esophageal cancer is the seventh most common cancer in the world. Although traditional treatment methods such as radiotherapy and chemotherapy have good effects, their side effects and drug resistance remain problematic. The repositioning of drug function provides new ideas for the research and development of anticancer drugs. We previously showed that the Food and Drug Administration-approved drug sulconazole can effectively inhibit the growth of esophageal cancer cells, but its molecular mechanism is not clear. Here, our study demonstrated that sulconazole had a broad spectrum of anticancer effects. It can not only inhibit the proliferation but also inhibit the migration of esophageal cancer cells. Both transcriptomic sequencing and proteomic sequencing showed that sulconazole could promote various types of programmed cell death and inhibit glycolysis and its related pathways. Experimentally, we found that sulconazole induced apoptosis, pyroptosis, necroptosis, and ferroptosis. Mechanistically, sulconazole triggered mitochondrial oxidative stress and inhibited glycolysis. Finally, we showed that low-dose sulconazole can increase radiosensitivity of esophageal cancer cells. Taken together, these new findings provide strong laboratory evidence for the clinical application of sulconazole in esophageal cancer.

Towards artificial intelligence to multi-omics characterization of tumor heterogeneity in esophageal cancer.

Esophageal cancer is a unique and complex heterogeneous malignancy, with substantial tumor heterogeneity: at the cellular levels, tumors are composed of tumor and stromal cellular components; at the genetic levels, they comprise genetically distinct tumor clones; at the phenotypic levels, cells in distinct microenvironmental niches acquire diverse phenotypic features. This heterogeneity affects almost every process of esophageal cancer progression from onset to metastases and recurrence, etc. Intertumoral and intratumoral heterogeneity are major obstacles in the treatment of esophageal cancer, but also offer the potential to manipulate the heterogeneity themselves as a new therapeutic strategy. The high-dimensional, multi-faceted characterization of genomics, epigenomics, transcriptomics, proteomics, metabonomics, etc. of esophageal cancer has opened novel horizons for dissecting tumor heterogeneity. Artificial intelligence especially machine learning and deep learning algorithms, are able to make decisive interpretations of data from multi-omics layers. To date, artificial intelligence has emerged as a promising computational tool for analyzing and dissecting esophageal patient-specific multi-omics data. This review provides a comprehensive review of tumor heterogeneity from a multi-omics perspective. Especially, we discuss the novel techniques single-cell sequencing and spatial transcriptomics, which have revolutionized our understanding of the cell compositions of esophageal cancer and allowed us to determine novel cell types. We focus on the latest advances in artificial intelligence in integrating multi-omics data of esophageal cancer. Artificial intelligence-based multi-omics data integration computational tools exert a key role in tumor heterogeneity assessment, which will potentially boost the development of precision oncology in esophageal cancer.

Distinguish Esophageal Cancer Cells through VOCs Induced by Methionine Regulation.

Detection of exhaled volatile organic compounds (VOCs) is promising for noninvasive screening of esophageal cancer (EC). Cellular VOC analysis can be used to investigate potential biomarkers. Considering the crucial role of methionine (Met) during cancer development, exploring associated abnormal metabolic phenotypes becomes imperative. In this work, we employed headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) to investigate the volatile metabolic profiles of EC cells (KYSE150) and normal esophageal epithelial cells (HEECs) under a Met regulation strategy. Using untargeted approaches, we analyzed the metabolic VOCs of the two cell types and explored the differential VOCs between them. Subsequently, we utilized targeted approaches to analyze the differential VOCs in both cell types under gradient Met culture conditions. The results revealed that there were five/six differential VOCs between cells under Met-containing/Met-free culture conditions. And the difference in levels of two characteristic VOCs (1-butanol and ethyl 2-methylbutyrate) between the two cell types intensified with the increase of the Met concentration. Notably, this is the first report on VOC analysis of EC cells and the first to consider the effect of Met on volatile metabolic profiles. The present work indicates that EC cells can be distinguished through VOCs induced by Met regulation, which holds promise for providing novel insights into diagnostic strategies.

Occupational asbestos exposure and risk of esophageal cancer: A systematic review and meta-analysis.

Esophageal cancer (EC), which includes squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), is an important cancer with poor prognosis and high mortality rate. Several occupational exposures have been associated with EC. We aim to investigate the association between occupational asbestos exposure and EC risk, considering types of asbestos and histology of the disease. We included studies mentioned in the list of references in previous reviews and pooled analyses, and we conducted an independent search in PubMed and Scopus. Forest plots of relative risks (RR) were constructed based on the association between occupational asbestos and EC risk. Random-effects models were used to address heterogeneity between 48 independent cohort and case-control studies. We found an association between occupational asbestos exposure and EC (meta-relative risk [RR] = 1.20, 95% confidence interval [CI] = 1.09-1.32; I2 = 58.8%, p-heterogeneity [het] <.001). The results of stratification by job (p-het = .20) indicate an increased RR among asbestos product workers (RR = 1.39, 95% CI = 1.07-1.81), asbestos applicators (RR = 1.41, 95% CI = 1.20-1.67), and construction workers (RR = 1.12, 95% CI = 1.02-1.24). There was no heterogeneity in meta-RR according to outcome (p = .29), geographic region (p = .69), year of publication (p = .59), quality score (p = .73), asbestos type (p = .93), study design (p = .87), and gender (p = .88), control for potential confounders (p = .20), year of first employment (p = .94) and exposure level (p = .43). The stratification analysis by histology type found an increased RR for both ESCC 1.33(1.03-1.71) and EAC 1.45(1.03-2.04) (p-het = .68). We didn't find evidence of publication bias (p = .07). The results of our study suggest that occupational asbestos exposure is associated with an increased risk of EC in both histology types.

Poor oral health and the risk of esophageal squamous cell carcinoma in Malawi.

Esophageal squamous cell carcinoma (ESCC) is the second most common cancer in Malawi. Risk factors for this cancer in Malawi are poorly understood. Poor oral health has previously been linked to increased ESCC risk in other high-incidence regions, including parts of Eastern and Southern Africa. We assessed the relationship between oral health and ESCC risk in a sex, age and location frequency-matched case-control study based at two hospitals in Lilongwe, Malawi from 2017 to 2020. Trained interviewers used a structured questionnaire and direct observation to collect data on demographics; behaviors; oral hygiene habits; the sum of decayed, missing or filled teeth (DMFT score); oral mucosa status; lip depigmentation and dental fluorosis via a visual scale. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI), adjusted for known and suspected ESCC risk factors. During the study period, 300 cases and 300 controls were enrolled. Subjects in the highest tertile of DMFT score (≥7) had an increased risk of ESCC with an adjusted OR of 1.96 (95% CI: 1.16-3.36) compared to those with a DMFT score of 0. Severe dental fluorosis was associated with a statistically nonsignificant increased risk of ESCC (adjusted OR = 2.24, 95% CI: 0.97-5.49) compared to individuals with no fluorosis. Associations with oral mucosa status, lip depigmentation and toothbrushing method and frequency were mostly null or uncertain. Poor oral health, indicated by a higher DMFT score, was associated with increased ESCC risk in Malawi. Dental fluorosis is another possible risk factor in this population, but further evaluation is necessary to clarify any effects of fluorosis on ESCC risk.

A narrative review on advances in neoadjuvant immunotherapy for esophageal cancer: Molecular biomarkers and future directions.

Esophageal cancer has a poor prognosis and survival rate due to its high incidence in Asia, lack of early symptoms and limited treatment options. In recent years, many clinical trials have demonstrated that immunotherapy has greatly improved the survival of patients with esophageal cancer. In addition, the combination of neoadjuvant immunotherapy with other popular therapeutic regimens has shown good efficacy and safety. In this review, we summarize the progress of clinical trials and some breakthroughs in neoadjuvant immunotherapy for esophageal cancer in recent years and suggest the possibility of multimodal neoadjuvant immunotherapy regimens, as well as directions for future development.

Analysis of the incidence and mortality trends of esophageal cancer in cancer registry areas of China and Japan.

This study aims to analyze the prevalence trend of esophageal cancer in Japan and China to provide suggestions for the prevention and treatment of esophageal cancer. The results showed that the incidence rate for the years 2010-2018 significantly decreased with an APC of 5.66%, and the mortality rate from 2010 to 2015 had an APC of -5.87% in China. However, the incidence rate of Japanese women showed an upward trend, with an APC of 4.09% from 2010 to 2019. The mortality rate of esophageal cancer in Japan showed a downward trend, with an APC of -2.96% from 2010 to 2021. From 2010 to 2018, Chinese esophageal squamous cell carcinoma accounted for the highest proportion, accounting for 85.96%, with the largest distribution in the middle, accounting for 47.25%. Patients are mostly diagnosed at stage III, and the relative survival rate from 2012 to 2015 was 30.3%. Japan also has the highest proportion of squamous cell carcinoma, and the lesions are also mostly located in the middle segment. While Japanese esophageal cancer patients are mostly diagnosed at stage I, and the relative survival rate was 41.5% in Japan from 2009 to 2011. The results of this article indicate that the current prevalence of esophageal cancer in China and Japan is generally declining, and the quality of life of patients is gradually improving, but effective screening and prevention strategies are still needed to reduce the burden of this disease.

The United States experience with diagnosing and treating esophageal cancer during the SARS-CoV-2 pandemic: A retrospective cohort study.

The downstream effects on healthcare delivery during the initial wave of the COVID-19 pandemic remain unclear. The purpose of this study was to determine how the healthcare environment surrounding the pandemic affected the oncologic care of patients diagnosed with esophageal cancer. This was a retrospective cohort study evaluating patients in the National Cancer Database (2019-2020). Patients with esophageal cancer diagnoses were divided into pre-pandemic (2019) and pandemic (2020) groups. Patient demographics, cancer-related variables, and treatment modalities were compared. Among 26,231 esophageal cancer patients, 14,024 patients (53.5%) were in the pre-pandemic cohort and 12,207 (46.5%) were in the pandemic cohort. After controlling for demographics, patients diagnosed during the pandemic were more likely to have poorly differentiated tumors (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.08-1.42), pathologic T3 disease compared to T1 (OR 1.25, 95% CI 1.02-1.53), positive lymph nodes on pathology (OR 1.36, 95% CI 1.14-1.64), and to be pathologic stage IV (OR 1.51, 95% CI 1.29-1.76). After controlling for oncologic characteristics, patients diagnosed during the pandemic were more likely to require at least two courses of systemic therapy (OR 1.78, 95% CI 1.48-2.14) and to be offered palliative care (OR 1.13, 95% CI 1.04-1.22). While these patients were offered curative therapy at lower rates, this became non-significant after risk-adjustment (p = .15). The pandemic healthcare environment was associated with significantly increased risk-adjusted rates of patients presenting with advanced esophageal cancer. While this led to significant differences in treatment, most of these differences became non-significant after controlling for oncologic factors.

One-carbon metabolism biomarkers and upper gastrointestinal cancer in the Golestan Cohort Study.

Incidence of esophageal and gastric cancer has been linked to low B-vitamin status. We conducted matched nested case-control studies of incident esophageal squamous cell carcinoma (ESCC; 340 case-control pairs) and gastric cancer (GC; 352 case-control pairs) within the Golestan Cohort Study. The primary exposure was plasma biomarkers: riboflavin and flavin mononucleotide (FMN) (vitamin B2), pyridoxal phosphate (PLP) (B6), cobalamin (B12), para-aminobenzoylglutamate (pABG) (folate), and total homocysteine (tHcy); and indicators for deficiency: 3-hydroxykyurenine-ratio (HK-r for vitamin B6) and methylmalonic acid (MMA for B12). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression adjusting for matching factors and potential confounders. High proportions of participants had low B-vitamin and high tHcy levels. None of the measured vitamin B levels was associated with the risk of ESCC and GC, but elevated level of MMA was marginally associated with ESCC (OR = 1.42, 95% CI = 0.99-2.04) and associated with GC (OR = 1.53, 95% CI = 1.05-2.22). Risk of GC was higher for the highest versus lowest quartile of HK-r (OR = 1.95, 95%CI = 1.19-3.21) and for elevated versus non-elevated HK-r level (OR = 1.59, 95% CI = 1.13-2.25). Risk of ESCC (OR = 2.81, 95% CI = 1.54-5.13) and gastric cancer (OR = 2.09, 95%CI = 1.17-3.73) was higher for the highest versus lowest quartile of tHcy. In conclusion, insufficient vitamin B12 was associated with higher risk of ESCC and GC, and insufficient vitamin B6 status was associated with higher risk of GC in this population with prevalent low plasma B-vitamin status. Higher level of tHcy, a global indicator of OCM function, was associated with higher risk of ESCC and GC.

The current infection with Helicobacter pylori and association with upper gastrointestinal lesions and risk of upper gastrointestinal cancer: Insights from multicenter population-based cohort study.

The relationship between Helicobacter pylori (H. pylori) infection and upper gastrointestinal (UGI) cancers is complex. This multicenter, population-based cohort study conducted in seven areas in China aimed to assess the correlation between current H. pylori infection and the severity of UGI lesions, as well as its association with the risk of gastric cancer (GC) and esophageal cancer (EC). From 2015 to 2017, 27,085 participants (aged 40-69) completed a standardized questionnaire, and underwent a 13C-urea breath test. Then a subset underwent UGI endoscopy to assess the UGI lesion detection rates. All individuals were followed up until December 2021 to calculate the hazard ratios (HRs) for UGI cancers. H. pylori infection prevalence was 45.9%, and among endoscopy participants, 22.2% had gastric lesions, 19.2% had esophageal lesions. Higher detection rates of gastric lesions were noted in the H. pylori-positive population across all lesion severity levels. Over a median follow-up of 6.3 years, 104 EC and 179 GC cases were observed, including 103 non-cardia gastric cancer (NCGC) cases and 76 cardia gastric cancer (CGC) cases. H. pylori-infected individuals exhibited a 1.78-fold increased risk of GC (HR 1.78, 95% confidence interval [CI] 1.32-2.40) but no significant increase in EC risk (HR 1.07, 95% CI 0.73-1.57). Notably, there was a higher risk for both NCGC and CGC in H. pylori-infected individuals. This population-based cohort study provides valuable evidence supporting the association between current H. pylori infection and the risk of both NCGC and CGC. These findings contribute to the empirical basis for risk stratification and recommendations for UGI cancer screening.