Search Results (114)

Chemotherapy remains a cornerstone in the treatment of esophageal cancer (EC), yet chemoresistance remains a critical challenge, leading to poor outcomes and limited therapeutic success. Mitochondrial DNA (mtDNA) has emerged as a pivotal player in mediating these responses, influencing cellular metabolism, oxidative stress regulation, and apoptotic pathways. This review provides a comprehensive overview of the mechanisms by which mtDNA alterations, including mutations and copy number variations, drive chemoresistance in EC. Specific focus is given to the role of mtDNA in metabolic reprogramming, including its contribution to the Warburg effect and lipid metabolism, as well as its impact on epithelial–mesenchymal transition (EMT) and mitochondrial bioenergetics. Recent advances in targeting mitochondrial pathways through novel therapeutic agents, such as metformin and mitoquinone, and innovative approaches like CRISPR/Cas9 gene editing, are also discussed. These interventions highlight the potential for overcoming chemoresistance and improving patient outcomes. By integrating mitochondrial diagnostics with personalized treatment strategies, we propose a roadmap for future research that bridges basic mitochondrial biology with translational applications in oncology. The insights offered in this review emphasize the critical need for continued exploration of mtDNA-targeted therapies to address the unmet needs in EC management and other diseases associated with mitochondria. Full article

Objectives: To investigate the real-world outcomes of a population-based gastric cancer (GC) screening program in Kawasaki City, a major urban area with a growing aging population and relatively high screening participation rates. Methods: Between December 2012 and 2021, a total of 337,842 citizens in Kawasaki City underwent population-based GC screening, leading to the detection of 1087 GC cases. Esophageal cancer (EC) has been recorded since 2016, with 236 cases detected. To evaluate the short- and long-term clinical outcomes of screening-detected GC and EC, we conducted a retrospective study using the electronic medical records of patients treated at our hospital, a high-volume institution for GC and EC treatment in the city. As a control group, we included 34 GC and EC cases diagnosed based on symptoms at our hospital in 2018. Results: Among the 1087 GC cases detected through population-based screening, 102 cases treated at our hospital were included in the analysis. Of them, 91 patients (89%) were diagnosed with early-stage GC. All screening-detected GC cases underwent either surgery (27 cases) or endoscopic submucosal dissection (75 cases). The five-year survival rates for GC were 90% in males and 86% in females. Eighteen EC cases were also included in the study. The five-year survival rate for screening-detected advanced GC was 70.0%, while for screening-detected EC, it was 100%. Both survival rates were significantly higher than those for symptom-diagnosed GC (30.0%) and EC (40.8%). Conclusions: The prognosis of GC and EC detected through population-based endoscopic screening is significantly better than that of cancers diagnosed based on symptoms. This underscores the effectiveness of endoscopic screening as a valuable tool for the early detection of upper gastrointestinal tract cancers. Full article

Objective: Esophageal cancer (EC) is difficult to visually identify, rendering early detection crucial to avert the advancement and decline of the patient’s health. Methodology: This work aimed to acquire spectral information from EC images via Spectrum-Aided Visual Enhancer (SAVE) technology, which improves imaging beyond the limitations of conventional White-Light Imaging (WLI). The hyperspectral data acquired using SAVE were examined utilizing sophisticated deep learning methodologies, incorporating models such as YOLOv8, YOLOv7, YOLOv6, YOLOv5, Scaled YOLOv4, and YOLOv3. The models were assessed to create a reliable detection framework for accurately identifying the stage and location of malignant lesions. Results: The comparative examination of these models demonstrated that the SAVE method regularly surpassed WLI for specificity, sensitivity, and overall diagnostic efficacy. Significantly, SAVE improved precision and F1 scores for the majority of the models, which are essential measures for enhancing patient care and customizing effective medicines. Among the evaluated models, YOLOv8 showed exceptional performance. YOLOv8 demonstrated increased sensitivity to squamous cell carcinomas (SCCs), but YOLOv5 provided reliable outcomes across many situations, underscoring its adaptability. Conclusions: These findings highlight the clinical importance of combining SAVE technology with deep learning models for esophageal cancer screening. The enhanced diagnostic accuracy provided by SAVE, especially when integrated with CAD models, offers potential for improving early detection, precise diagnosis, and tailored treatment approaches in clinically pertinent scenarios. Full article

(1) Objective: Cold atmospheric plasma (CAP) is a safe and effective alternative to radiotherapy for cancer treatment. Its anticancer effects are attributed to increased intracellular reactive oxygen species (ROS). Glutathione, a key antioxidant derived from glutamine, is critical for cell proliferation. This study investigated whether CAP-induced ROS elevation results from reduced glutamine–glutathione conversion and elucidates the underlying mechanisms. (2) Methods: Using esophageal squamous carcinoma cell models (Ec9706 and Eca109), we analyzed CAP’s effects on key enzymes in glutamine metabolism (Glutaminase 1 and γ-glutamylcysteine ligase) and proliferation-related genes (e.g., Retinoblastoma and Nuclear respiratory factor 2). Transcriptome analysis further explored molecular pathways involved in CAP-mediated anticancer effects. (3) Results: CAP reduced Glutaminase 1 and γ-glutamylcysteine ligase expression, leading to lower intracellular glutathione, higher ROS activity, and enhanced apoptosis. Transcriptome data confirmed CAP’s role in oxidation-reduction reactions and glutamine metabolism. (4) Conclusions: This study provides the first mechanistic insights into CAP’s anticancer effects by targeting glutamine metabolism. While based on in vitro assays, these findings guide the development of novel CAP therapies for currently incurable cancers. Full article

Objective: Esophageal carcinoma (EC) is the eighth most prevalent cancer and the sixth leading cause of cancer-related mortality worldwide. Early detection is vital for improving prognosis, particularly for dysplasia and squamous cell carcinoma (SCC). Methods: This study evaluates a hyperspectral imaging conversion method, the Spectrum-Aided Vision Enhancer (SAVE), for its efficacy in enhancing esophageal cancer detection compared to conventional white-light imaging (WLI). Five deep learning models (YOLOv9, YOLOv10, YOLO-NAS, RT-DETR, and Roboflow 3.0) were trained and evaluated on a dataset comprising labeled endoscopic images, including normal, dysplasia, and SCC classes. Results: Across all five evaluated deep learning models, the SAVE consistently outperformed conventional WLI in detecting esophageal cancer lesions. For SCC, the F1 score improved from 84.3% to 90.4% in regard to the YOLOv9 model and from 87.3% to 90.3% in regard to the Roboflow 3.0 model when using the SAVE. Dysplasia detection also improved, with the precision increasing from 72.4% (WLI) to 76.5% (SAVE) in regard to the YOLOv9 model. Roboflow 3.0 achieved the highest F1 score for dysplasia of 64.7%. YOLO-NAS exhibited balanced performance across all lesion types, with the dysplasia precision rising from 75.1% to 79.8%. Roboflow 3.0 also recorded the highest SCC sensitivity of 85.7%. In regard to SCC detection with YOLOv9, the WLI F1 score was 84.3% (95% CI: 71.7–96.9%) compared to 90.4% (95% CI: 80.2–100%) with the SAVE (p = 0.03). For dysplasia detection, the F1 score increased from 60.3% (95% CI: 51.5–69.1%) using WLI to 65.5% (95% CI: 57.0–73.8%) with SAVE (p = 0.04). These findings demonstrate that the SAVE enhances lesion detectability and diagnostic performance across different deep learning models. Conclusions: The amalgamation of the SAVE with deep learning algorithms markedly enhances the detection of esophageal cancer lesions, especially squamous cell carcinoma and dysplasia, in contrast to traditional white-light imaging. This underscores the SAVE’s potential as an essential clinical instrument for the early detection and diagnosis of cancer. Full article

Background: Esophageal cancer (EC) is the eighth most common cancer and the sixth most common cause of death worldwide. Esophageal squamous cell carcinoma (ESCC) comprises the majority of esophageal cancers globally, and 5-Fluorouraci (5-FU) is one of the commonly used chemotherapeutics for this type of cancer. Chemoresistance to drugs is a main obstacle in the successful treatment of this malignancy. Methods: In this study, we used the CRISPR/Cas9 screening method to determine the target gene related to 5-FU drug resistance in esophageal cancer. Results: Our research findings indicate that the loss of PFKFB3 can increase the resistance of different human esophageal squamous cell carcinoma cell lines to 5-FU through various pathways. Specifically, in KYSE-70 cells, loss of PFKFB3 can induce epithelial–mesenchymal transition (EMT) and prolong the S phase of the cell cycle, allowing cancer cells to evade the effects of 5-FU and develop resistance. In the KYSE-270 and KYSE-150 cell lines, loss of PFKFB3 can upregulate the expression of Slug and Mcl-1, indirectly regulate Chk1 and promote its autophosphorylation, which in turn inhibits apoptosis, thus counteracting the effects of 5-FU. Conclusions: Our research not only enriches our understanding of the biological characteristics of different ESCC cell lines but also provides new clinical insights for future personalized treatments. Assessing the status of PFKFB3 can help predict resistance to 5-FU in ESCC patients with different genetic backgrounds, allowing for more precise treatment planning. This personalized approach has the potential to improve treatment efficacy, reduce unnecessary drug use and side effects, and ultimately improve patient survival rates and quality of life. Full article

Esophageal cancer (EC) is the eighth leading cause of cancer-related deaths globally, largely due to its late-stage diagnosis and aggressive progression. Esophagectomy remains the primary treatment, typically requiring organ-based reconstruction techniques such as gastric pull-up or colonic interposition. However, these reconstruction methods often lead to severe complications, significantly reducing the quality of life of patients. To address these limitations, tissue engineering has emerged as a promising alternative, offering bioengineered patch-type and tubular-type scaffolds designed to restore both structural integrity and functional regeneration. Recent advancements in three-dimensional (3D) biofabrication—including 3D bioprinting, electrospinning, and other cutting-edge techniques—have facilitated the development of patient-specific constructs with improved biocompatibility. Despite significant advancements, critical challenges persist in achieving mechanical durability, multilayered cellular organization, and physiological resilience post-transplantation. Ongoing research continues to address these limitations and enhance clinical applicability. Therefore, this review aims to examine recent advancements in esophageal tissue engineering, with a focus on key biofabrication techniques, preclinical animal models, and the major translational challenges that must be addressed for successful clinical application. Full article

This review provides an in-depth analysis and comprehensive overview of recent advancements in MRI techniques for evaluating esophageal cancer (EC). It discusses the specific MRI acquisition protocols and parameters that enhance image quality and diagnostic accuracy. The review highlights MRI’s role and performance in the initial TNM staging and its potential to refine treatment strategies by improving tumor delineation and characterization. Additionally, the paper explores MRI utility in restaging after NAT, focusing on its accuracy in assessing treatment response and detecting residual or recurrent disease. Comparisons with other imaging modalities currently used—such as endoscopic ultrasound (EUS), contrast-enhanced computed tomography (CE-CT), and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT)—are included to highlight the strengths and limitations of each method. Illustrated with numerous Figures, this article proposes a novel MRI-based strategy for EC staging and restaging. It aims to integrate MRI into clinical practice by leveraging its superior soft-tissue contrast and functional imaging capabilities to enhance diagnostic precision and improve patient outcomes. Through this comprehensive evaluation, the review underscores the potential of MRI to become a cornerstone in the precision diagnosis and management of EC. Full article

Background/Objectives: Esophageal cancer (EC) represents a major global contributor to cancer-related mortality. The advent of artificial intelligence (AI), including machine learning, deep learning, and radiomics, holds promise for enhancing treatment decisions and predicting outcomes. The aim of this review is to present an overview of the current landscape and future perspectives of AI in the management of EC. Methods: A literature search was performed on MEDLINE using the following keywords: “Artificial Intelligence”, “Esophageal cancer”, “Barrett’s esophagus”, “Esophageal Adenocarcinoma”, and “Esophageal Squamous cell carcinoma”. All titles and abstracts were screened; the results included 41 studies. Results: Over the past five years, the number of studies focusing on the application of AI to the treatment and prognosis of EC has surged, leveraging increasingly larger datasets with external validation. The simultaneous incorporation in AI models of clinical factors and features from several imaging modalities displays improved predictive performance, which may enhance patient outcomes, based on direct personalized therapeutic options. However, clinicians and researchers must address existing limitations, conduct randomized controlled trials, and consider the ethical and legal aspects that arise to establish AI as a standard decision-support tool. Conclusions: AI applications may result in substantial advances in EC management, heralding a new era. Considering the complexity of EC as a clinical entity, the evolving potential of AI is anticipated to ameliorate patients’ quality of life and survival rates. Full article

Background/Objectives: Percutaneous endoscopic gastrostomy (PEG) is recommended for long-term enteral nutrition in dysphagic patients. This study aims to characterize conditions motivating PEG, assess nutritional status on the gastrostomy day, evaluate survival and search for survival predictors. Methods: Retrospective study of adult patients who underwent PEG in a tertiary hospital from 2001 to 2023. Data collected included demographics, underlying disorders, nutritional status (anthropometry/laboratory evaluation) on the day of PEG and survival recorded until death or December 2023. Multivariable analysis was performed with Cox regression to search for survival predictors. Results: A total of 1415 patients were included (61.8% males, mean age 66.9 years); 66.4% presented a neurological disorder and 31.3% head and neck or esophageal cancers (HNC/EC). The mean BMI was 20.9 kg/m², with 49.8% underweight. Albumin, transferrin and total cholesterol were low at 43.2%, 62.2% and 50%, respectively. Median overall survival was 11.1 months; 14.1% of deaths occurred within 4 weeks. HNC/EC patients showed lower survival than neurological patients. Potentially regressive neurological conditions presented longer survival than progressive ones. Predictors of increased survival included female gender, younger age, higher albumin and higher BMI. The protective effect of BMI and albumin was more pronounced in males than in females. Conclusions: Neurological disorders were the most frequent underlying conditions. Nearly half of the patients displayed malnutrition before PEG feeding. Although PEG-fed patients displayed a considerable median survival time, some died early without benefit from PEG. Patients with potentially regressive neurological conditions presented better outcomes. Female gender, younger age, higher albumin and higher BMI were associated with longer survival. Full article

The prevalence and deaths from esophageal cancer (EC) have recently increased. Although therapeutic strategies depend on the EC stage and recurrence, such as surgical intervention, chemotherapy, radiation therapy, chemoradiation therapy, targeted therapy, and immunotherapy, a more effective and novel treatment for EC is still required. This review briefly describes and summarizes some insightful oncotargets involved in the metabolic modulation of EC, including (1) cancer stem cells (CSCs) for EC progression, poor prognosis, tumor recurrence, and therapy resistance; (2) retinoic acid receptors (RARs) for esophageal carcinogenesis and regeneration; (3) phosphofructokinase (PFK) for EC-reprogrammed glycolysis; (4) lactate dehydrogenase (LDH) as an EC peripheral blood biomarker; and (5) hypoxia-inducible factor-1 alpha (HIF-1α) for the tumor microenvironment under hypoxic conditions. Moreover, the aforementioned oncotargets can be modulated by mutant TP53 and have their own features in the carcinogenesis, differentiation, proliferation, and metastasis of EC. Thus, the clarification of pharmacological mechanisms regarding the interaction between mutant TP53 and the abovementioned oncotargets could provide precise and perspective opinions for minimizing prediction errors, reducing therapy resistance, and developing novel drugs against EC. Full article

Background/Objectives: The management of esophageal cancer (EC) remains a significant clinical challenge, particularly in optimizing therapeutic strategies for different stages and subgroups. This study assessed the impact of preoperative radiochemotherapy (CRT) on clinical staging and identified subgroups for whom definitive CRT (dCRT) may provide a favorable alternative to surgery. Methods: Sixty-one patients with esophageal adenocarcinoma or squamous cell carcinoma were enrolled. Pre-treatment staging included computed tomography, gastroscopy with biopsy, and comprehensive laboratory evaluations. Patients received preoperative CRT following the CROSS or dCRT protocols based on tumor stage. Surgical approaches included staged esophagectomy or single-stage Ivor Lewis procedures. Four patients declined surgery and were treated with dCRT. Postoperative outcomes were evaluated using pTNM classification. Follow-up included imaging and endoscopic surveillance. Statistical analyses assessed changes in staging and factors influencing treatment outcomes. Results: CRT significantly reduced T stage across the entire cohort (p = 0.0002), with complete pathological response (pT0N0M0) observed in 54.5% of patients following induction CRT (p = 0.0001). Male patients demonstrated a significant reduction in T stage (p = 0.0008), while a similar trend in females was not significant (p = 0.068). Among patients declining surgery, dCRT demonstrated acceptable oncologic control over a mean follow-up of 4 ± 0.79 years. Conclusions: Preoperative CRT effectively downstages EC and achieves high rates of response, especially in male patients. Therefore, dCRT may be a viable alternative in selected patients, emphasizing the need for individualized treatment strategies to optimize outcomes. These findings underscore the importance of refining multimodal approaches in EC care. Full article

Esophageal cancer (EC) is one of the leading causes of cancer-related deaths globally. Surgery is the standard treatment for resectable EC after preoperative chemoradiotherapy or chemotherapy, followed by postoperative adjuvant chemotherapy in certain cases. Upper gastrointestinal endoscopy and computed tomography (CT) are predominantly performed to evaluate the efficacy of these treatments, but their sensitivity and accuracy for evaluating minimal residual disease remain unsatisfactory, thereby requiring the development of alternative methods. In recent years, interest has been increasing in using liquid biopsy to assess treatment responses. Liquid biopsy is a noninvasive technology for detecting cell components in the blood and other body fluids. It involves collecting a small sample of body fluid, which is then analyzed for the presence of components, including circulating tumor DNA (ctDNA), microRNA (miRNA), or circulating tumor cells (CTCs). Further, ctDNA and miRNA are analyzed with various techniques, including digital polymerase chain reaction (dPCR) and next-generation sequencing (NGS). CTCs are isolated by determining surface antigens using immunomagnetic techniques or by filtering the blood according to cell size and rigidity. Several studies indicate that investigating these materials helps predict EC prognosis and recurrence and possibly stratifies high-risk groups. Liquid biopsy may also apply to the selection of cases that have achieved a complete response through preoperative treatment to prevent surgery and preserve the esophagus, as well as identifying the suitability of postoperative chemotherapy and the timing of conversion surgery for unresectable EC. The potential of liquid biopsy to enhance treatment decisions will further advance EC treatment. Full article

Background: Esophageal cancer (EC) is the sixth leading cause of cancer-related mortality worldwide, continuing to be a significant public health concern. The purpose of this study is to assess the impact of staging and histopathology of EC on associated mortality. The study also aims to further investigate clinical characteristics, prognostic factors, and survival outcomes in patients diagnosed with EC between 2010 and 2017. Furthermore, we analyzed the interaction between tumor histology and staging and the risk of mortality. Methods: A total of 24,011 patients diagnosed with EC between 2010 and 2017 in the United States were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Demographic parameters, tumor stage, and histologic subtypes were analyzed and associated overall mortality (OM) and cancer-specific mortality (CSM) were measured across all subgroups. Covariates reaching the level of statistical significance, demonstrable by a p-value equal to or less than 0.01, were incorporated into a multivariate Cox proportional hazards model. A hazard ratio greater than 1 was indicative of an increased risk of mortality in the presence of the variable under discussion. Additionally, the study explores the interaction between histology and tumor stage on outcomes. Results: The majority of patients were male (80.13%) and non-Hispanic white (77.87%), with a predominant age at diagnosis of between 60 and 79 years (59.86%). Adenocarcinoma was the most common tumor subtype (68.17%), and most patients were diagnosed at a distant stage (41.29%). Multivariate analysis revealed higher mortality risks for males, older patients, unmarried individuals, and those with advanced-stage tumors. Higher income, receiving radiation or chemotherapy, and undergoing surgery were associated with lower mortality. Tumor subtype significantly influenced mortality, with squamous cell carcinoma and neuroendocrine tumors showing higher hazard ratios compared to adenocarcinoma. Adenocarcinoma is linked to a poorer prognosis at advanced stages, whereas the opposite trend is observed for SCC. Conclusions: The study identifies significant demographic and clinicopathologic factors influencing mortality in esophageal cancer patients, highlighting the importance of early diagnosis and treatment intervention. Future research should focus on tailored treatment strategies to improve survival outcomes in high-risk groups and to understand the interaction between tumor histology and tumor stage. Full article

Background and Objectives: Temperature-sensitive (TS) mutants of TP53 are thermally unstable, unfolded, and inactive at body temperature but can be refolded and reactivated at sub-physiological temperatures. TS TP53 may be amenable for functional rescue by hypothermia or structure-stabilizing drugs, and may retain low-level transcriptional activity at 37 °C. TP53 mutations are observed in 47% of all esophageal cancers (ECs) and 25% to 40% of gastric cancers (GCs). We aimed to investigate the trends and outcomes of EC and GC with TS TP53 mutations using cBioportal. We hypothesize that TS TP53 mutants in EC and GC present a unique prognostic profile distinct from non-TS TP53 mutants, potentially affecting overall survival and cancer progression. Materials and Methods: We identified 1924 patients from cBioportal with GC or EC, harboring any TP53 mutation. Patients were then stratified based on the TP53 temperature sensitivity according to a recently reported functional analysis of its activity. Patients were also stratified based on a history of Barrett’s esophagus (BE), cancer stage, sex, and race. We then compared populations (TS vs. non-TS TP53) to assess differences and evaluated survival outcomes. Results: Males represented 77% of the cohort, and 51.6% of the samples were from patients with stage IV cancer. No association was found between TS vs. non-TS mutational status and BE, cancer stage, or race. Interestingly, a significantly higher proportion of females (22.9%) than males (14.5%) displayed a TS TP53 mutation (p = 0.012). No significant difference was seen in overall survival between the TS and non-TS mutations capable of ≥50% growth suppression at 32 °C (median = 33 vs. 28 months, p = 0.36). This trend was also observed when the patients were filtered based on cancer location. The median survival for EC was 32.5 months compared to 33 months (p = 0.67). In cases of GC, median survival times could not be determined due to the insufficient number of events. Conclusions: Although no statistical significance was observed, a decrease in overall survival for patients with TS TP53 mutations was noted. The result is counterintuitive given that TS mutants have less severe structural destabilization and suggests TS TP53 mutations may have a unique prognostic value that warrants further investigation. Full article