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Keywords = Barrett's esophagus

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13 pages, 1157 KiB  
Review
Precision Care in Screening, Surveillance, and Overall Management of Barrett’s Esophagus
by Yeshaswini Reddy, Madhav Desai, Bernadette Tumaliuan and Nirav Thosani
J. Pers. Med. 2025, 15(8), 327; https://doi.org/10.3390/jpm15080327 - 22 Jul 2025
Viewed by 351
Abstract
Barrett’s esophagus (BE), a metaplastic transformation of an esophageal squamous epithelium into an intestinal-type columnar epithelium, is the primary precursor to esophageal adenocarcinoma (EAC). Traditional management strategies have relied heavily on selective screening, tailored surveillance intervals, and early dysplasia detection and treatment algorithms. [...] Read more.
Barrett’s esophagus (BE), a metaplastic transformation of an esophageal squamous epithelium into an intestinal-type columnar epithelium, is the primary precursor to esophageal adenocarcinoma (EAC). Traditional management strategies have relied heavily on selective screening, tailored surveillance intervals, and early dysplasia detection and treatment algorithms. However, the heterogeneity in progression risk among BE patients necessitates a more nuanced, personalized approach involving precision care, tailoring decisions to individual patient characteristics, promises to enhance outcomes in BE through more targeted screening, personalized surveillance intervals, and risk-based therapeutic strategies. This review explores the current landscape and emerging trends in precision medicine for Barrett’s esophagus, highlighting genomic markers, digital pathology, and AI-driven models as tools to transform how we approach this complex disease and prevent progression to EAC. Full article
(This article belongs to the Special Issue Clinical Updates on Personalized Upper Gastrointestinal Endoscopy)
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12 pages, 1075 KiB  
Perspective
Strategy for Mitigating the Worldwide Burden of Gastroesophageal Reflux Disease—A European Medical Association Position Paper Endorsing Innovation in Laparoscopic Surgery for Sustainable Management
by Luigi Bonavina, Guglielmo Trovato, Rosario Caruso, Prisco Piscitelli, Alberto Aiolfi, Rosario Squatrito, Roberto Penagini, Davide Bona, Giovanni Dapri and Jerome R. Lechien
Therapeutics 2025, 2(3), 12; https://doi.org/10.3390/therapeutics2030012 - 3 Jul 2025
Viewed by 394
Abstract
Background and Aims: Gastroesophageal reflux disease (GERD) is the most common esophageal disorder worldwide and a progressive condition leading to Barrett’s esophagus and adenocarcinoma. Continuous medical therapy with proton pump inhibitors fails to restore the antireflux barrier and is unable to relieve symptoms [...] Read more.
Background and Aims: Gastroesophageal reflux disease (GERD) is the most common esophageal disorder worldwide and a progressive condition leading to Barrett’s esophagus and adenocarcinoma. Continuous medical therapy with proton pump inhibitors fails to restore the antireflux barrier and is unable to relieve symptoms in up to 40% of patients. A tailored and standardized antireflux surgical procedure may increase cure rates and meet patient expectations. Methods and Results: Antireflux surgery aims to reestablish the natural antireflux barrier, which includes the diaphragmatic crura, the lower esophageal sphincter (LES), and the angle of His along with the gastroesophageal flap valve. For decades, the Nissen total fundoplication has been the primary procedure and remains the gold standard for surgical treatment. Alternatives such as Toupet partial fundoplication, Dor partial fundoplication, and the magnetic sphincter augmentation (LINX™) procedure have been developed to mitigate side effects like dysphagia, gas-bloat syndrome, and the inability to belch or vomit. Recent clinical findings regarding a novel procedure, RefluxStop™, indicate that restoring the gastroesophageal flap valve, in conjunction with anterior fundoplication and a silicone device for stabilizing the LES beneath the diaphragm, can achieve lasting reflux control and enhance patient-reported outcomes. Conclusions: The planning of healthcare services and actionable strategies to improve equity and quality of treatment is critical to address the global burden of GERD. Modern laparoscopic surgery for GERD is safe and effective and should be performed in centers offering a complete diagnostic pathway and specific surgical techniques tailored to the individual GERD phenotype. Shared decision-making between the surgeon and the patient is essential for the choice of operation. A personalized approach can offer clinical benefits over total fundoplication and improve patient-reported outcomes. Full article
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19 pages, 993 KiB  
Article
Amprenavir Mitigates Pepsin-Induced Transcriptomic Changes in Normal and Precancerous Esophageal Cells
by Pelin Ergun, Tina L. Samuels, Angela J. Mathison, Tianxiang Liu, Victor X. Jin and Nikki Johnston
Int. J. Mol. Sci. 2025, 26(13), 6182; https://doi.org/10.3390/ijms26136182 - 26 Jun 2025
Viewed by 621
Abstract
Gastroesophageal reflux disease (GERD) is associated with inflammatory and neoplastic changes in the esophageal epithelium. Despite widespread PPI use, esophageal adenocarcinoma (EAC) incidence continues to rise, implicating non-acidic reflux components such as pepsin in disease progression. We performed transcriptomic profiling to assess pepsin-induced [...] Read more.
Gastroesophageal reflux disease (GERD) is associated with inflammatory and neoplastic changes in the esophageal epithelium. Despite widespread PPI use, esophageal adenocarcinoma (EAC) incidence continues to rise, implicating non-acidic reflux components such as pepsin in disease progression. We performed transcriptomic profiling to assess pepsin-induced changes and the protective effect of amprenavir in vitro. Het-1A (normal) and BAR-T (Barrett’s) cells (n = 3) were treated at pH 7.0 with pepsin and/or 10 μM amprenavir for 1 h. RNA-seq identified DEGs (FDR ≤ 0.05, |log₂FC| ≥ 0.375), and Ingenuity Pathway Analysis revealed enriched pathways. Pepsin exposure altered mitochondrial function, oxidative phosphorylation, epithelial integrity, signaling, and inflammatory pathways in both cell lines. Amprenavir attenuated these transcriptomic perturbations, preserving mitochondrial and stress-response pathways. Notably, BAR-T cells exhibited heightened activation of wound-healing and epithelial repair pathways, whereas Het-1A cells showed greater mitochondrial and systemic stress pathway alterations. Pepsin drives transcriptomic dysregulation in esophageal epithelial cells under non-acidic conditions, and amprenavir shows potential to counteract peptic injury. Further studies are needed to validate these findings and explore amprenavir’s therapeutic utility in GERD management and EAC prevention. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Esophageal Inflammation, Injury, and Repair)
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15 pages, 525 KiB  
Review
The Oncogenic Burden of Obesity: Mechanistic Links Between Adiposity and Gastrointestinal Cancers—A Comprehensive Narrative Review
by Felicia Lee, Jessica Moore, Mariam Markouli and Wissam Ghusn
Biomedicines 2025, 13(7), 1571; https://doi.org/10.3390/biomedicines13071571 - 26 Jun 2025
Viewed by 908
Abstract
Obesity is a global health crisis with profound implications for cancer risk, particularly within the gastrointestinal (GI) tract. Mounting evidence demonstrates that excess adiposity contributes to the initiation, progression, and poor outcomes of GI malignancies through a constellation of interrelated mechanisms. This review [...] Read more.
Obesity is a global health crisis with profound implications for cancer risk, particularly within the gastrointestinal (GI) tract. Mounting evidence demonstrates that excess adiposity contributes to the initiation, progression, and poor outcomes of GI malignancies through a constellation of interrelated mechanisms. This review comprehensively examines the biologic pathways linking obesity to cancers of the esophagus, stomach, colon, liver, pancreas, and gallbladder. Chronic low-grade inflammation, driven by adipose tissue-derived cytokines and immune cell infiltration, plays a central role in tumorigenesis via the activation of NF-κB, STAT3, and other pro-oncogenic signaling cascades. Hyperinsulinemia and insulin resistance increase mitogenic IGF-1 signaling, while dysregulated adipokines, particularly elevated leptin and reduced adiponectin, promote cellular proliferation and impair tumor suppression. Dysbiosis of the gut microbiome and alterations in bile acid metabolism generate carcinogenic metabolites that contribute to DNA damage and immune evasion. Additionally, obesity-induced tissue hypoxia fosters tumor growth through HIF-1α-mediated pathways. We further highlight organ-specific associations, such as visceral adiposity’s role in Barrett’s esophagus and hepatocellular carcinoma emerging from metabolic dysfunction-associated steatotic liver disease (MASLD). Importantly, emerging data suggest that weight loss, achieved via lifestyle, pharmacologic, or surgical interventions, may mitigate these carcinogenic pathways and improve tumor biology. As obesity prevalence continues to rise globally, elucidating its mechanistic ties to GI malignancies is essential for risk stratification, prevention strategies, and personalized care. By integrating epidemiologic and molecular insights, this review underscores the need for multidisciplinary approaches to curb the oncogenic burden of obesity and improve outcomes in GI oncology. Full article
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16 pages, 803 KiB  
Review
The Role of Microbiota in Upper Gastrointestinal Cancers
by Giovanni Marasco, Luigi Colecchia, Daniele Salvi, Angelo Bruni, Cecilia Capelli, Elton Dajti, Maria Raffaella Barbaro, Cesare Cremon, Vincenzo Stanghellini and Giovanni Barbara
Cancers 2025, 17(10), 1719; https://doi.org/10.3390/cancers17101719 - 21 May 2025
Viewed by 875
Abstract
The gut microbiota significantly impacts the development and progression of upper gastrointestinal (GI) cancers, including esophageal and gastric cancers. Microbial dysbiosis contributes to carcinogenesis through mechanisms such as inflammation, immune modulation, and direct DNA damage. Techniques for sampling oral, esophageal, and gastric microbiota [...] Read more.
The gut microbiota significantly impacts the development and progression of upper gastrointestinal (GI) cancers, including esophageal and gastric cancers. Microbial dysbiosis contributes to carcinogenesis through mechanisms such as inflammation, immune modulation, and direct DNA damage. Techniques for sampling oral, esophageal, and gastric microbiota vary, with standardization being essential for reliable results. Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) are associated with an enrichment of Gram-negative bacteria, promoting inflammation and cancer progression. Esophageal squamous cell carcinoma (ESCC) also shows distinct microbial patterns, with reduced diversity and increased harmful bacteria like Porphyromonas gingivalis and Fusobacterium nucleatum. In gastric cancer (GC), Helicobacter pylori (HP) and non-HP gastric microbiota play significant roles, with diverse microbial communities contributing to cancer development through nitrate reduction, immune modulation, and inflammation. Emerging evidence highlights the role of non-HP bacteria in promoting carcinogenesis, with specific taxa like Fusobacterium nucleatum and Lactobacillus influencing tumor growth and immune evasion. Further research is needed to elucidate the complex interactions between gut microbiota and upper GI cancers, paving the way for novel diagnostic and therapeutic approaches. Understanding these microbial dynamics offers potential for microbiota-based interventions, improving the early detection, prognosis, and treatment of upper GI cancers. This comprehensive review summarizes the available evidence on the role of microbiota in upper GI oncology and the need for continued exploration in this field. Full article
(This article belongs to the Special Issue Developments in the Management of Gastrointestinal Malignancies)
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18 pages, 469 KiB  
Review
Transforming Gastrointestinal Diagnosis with Molecular Endoscopy: Challenges and Opportunities
by Giuseppe Dell’Anna, Francesco Mandarino, Lucia Centanni, Ilaria Lodola, Jacopo Fanizza, Ernesto Fasulo, Sarah Bencardino, Lorenzo Fuccio, Antonio Facciorusso, Gianfranco Donatelli, Tommaso Lorenzo Parigi, Federica Furfaro, Ferdinando D’Amico, Sara Massironi, Alberto Malesci, Federica Ungaro, Silvio Danese and Vito Annese
Int. J. Mol. Sci. 2025, 26(10), 4834; https://doi.org/10.3390/ijms26104834 - 18 May 2025
Viewed by 748
Abstract
Molecular endoscopy represents a transformative advance in the detection, diagnosis, and management of gastrointestinal diseases, addressing the critical limitations of conventional techniques. Current diagnostic standards, such as white light endoscopy (WLE), often fail to detect early-stage lesions, particularly in high-risk populations like Barrett’s [...] Read more.
Molecular endoscopy represents a transformative advance in the detection, diagnosis, and management of gastrointestinal diseases, addressing the critical limitations of conventional techniques. Current diagnostic standards, such as white light endoscopy (WLE), often fail to detect early-stage lesions, particularly in high-risk populations like Barrett’s esophagus or inflammatory bowel disease patients. To overcome these challenges, molecular endoscopy, using fluorescent molecular probes, may offer ultimate precision by targeting disease-specific biomarkers. Technologies like Confocal Laser Endomicroscopy (CLE) and Immunoendoscopy are revolutionizing in vivo diagnostics, enabling the real-time visualization of tissue microarchitecture and physiological mechanisms. Fluorescence molecular endoscopy (FME) enhances the detection of precancerous and cancerous lesions, even those undetectable by conventional methods, by highlighting subtle molecular changes. Clinical applications include early tumor detection, therapy response monitoring, and improved lesion characterization. Despite these advancements, challenges persist, including high costs, a lack of standardization, and the need for specialized training. Recent innovations, such as a multi-parametric rigid standard, aim to ensure the reliable performance assessment and quality control of FME systems, addressing subjective variability and improving reproducibility. In addition, the integration of artificial intelligence (AI) with molecular endoscopy offers the potential to further reduce detection errors and significantly enhance diagnostic accuracy. This advancement underscores the potential of molecular endoscopy for personalized GI disease management, while highlighting the need for ongoing research to refine the technology, validate its clinical utility, and overcome the barriers to routine clinical application. Full article
(This article belongs to the Special Issue Focus on Gastrointestinal Diseases: Inflammation, 3rd Edition)
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31 pages, 1034 KiB  
Review
Updates in Gastroesophageal Reflux Disease Management: From Proton Pump Inhibitors to Dietary and Lifestyle Modifications
by Jakov Ivan Bucan, Tamara Braut, Antea Krsek, Vlatka Sotosek and Lara Baticic
Gastrointest. Disord. 2025, 7(2), 33; https://doi.org/10.3390/gidisord7020033 - 30 Apr 2025
Viewed by 4551
Abstract
Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that greatly influences patients’ quality of life and represents a growing public health concern. Characterized by typical and atypical symptoms, GERD encompasses a range of clinical phenotypes and is associated with complications such [...] Read more.
Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that greatly influences patients’ quality of life and represents a growing public health concern. Characterized by typical and atypical symptoms, GERD encompasses a range of clinical phenotypes and is associated with complications such as erosive esophagitis and Barrett’s esophagus. This review intends to provide a thorough overview of current scientific knowledge on the etiological factors, risk determinants, and pathophysiology of GERD, while exploring diagnostic challenges and therapeutic approaches. Proton pump inhibitors (PPIs) remain the mainstay of medical therapy; however, concerns regarding their long-term safety have encouraged interest in adjunctive and alternative strategies. Emerging pharmacological agents, plant-based treatments, and integrative approaches rooted in traditional medicine offer promising modalities for enhanced management. Additionally, dietary and lifestyle modifications such as weight control, meal timing, and avoidance of trigger foods, are essential components of effective care. A multidisciplinary framework incorporating pharmacological, nutritional, and behavioral strategies is emphasized as the most reliable path toward personalized and sustainable GERD management. This review further aims to synthesize current therapeutic modalities and evolving perspectives in the treatment of GERD. Full article
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11 pages, 1823 KiB  
Article
Characteristics and Neoplastic Progression in Barrett’s Esophagus: A Large Population-Based Study from Iceland
by Ken Namikawa, Melkorka Sverrisdottir, Hilmar Freyr Fridgeirsson, Hjalti Dagur Hjaltason, Helgi Kristinn Sigmundsson, Jon Gunnlaugur Jonasson, Einar Stefan Bjornsson and Magnus Konradsson
Diagnostics 2025, 15(6), 684; https://doi.org/10.3390/diagnostics15060684 - 11 Mar 2025
Viewed by 1302
Abstract
Background: Barrett’s esophagus (BE) is a known precursor to esophageal adenocarcinoma (EAC). However, reports on incidence and progression-to-neoplasm rates have been very variable and conflicting. The aims of the study were to evaluate the characteristics of BE and its progression to neoplasm in [...] Read more.
Background: Barrett’s esophagus (BE) is a known precursor to esophageal adenocarcinoma (EAC). However, reports on incidence and progression-to-neoplasm rates have been very variable and conflicting. The aims of the study were to evaluate the characteristics of BE and its progression to neoplasm in a large homogeneous population. Methods: This was a retrospective population-based study with patients identified from 11 institutions through the databases in two centralized pathology laboratories. Demographics and relevant clinicopathological features were obtained from medical records among patients with a pathologically confirmed BE by the presence of intestinal metaplasia between 2003 and 2022. Results: A total of 1388 patients were identified with BE: 948 were men (69%); the median age at diagnosis was 62 years (IQR, 53–72). The ratio of long-segment BE to short-segment BE was significantly higher in patients ≥ 60 years (1.15, 284/248) than those ≤ 60 years (0.77, 205/265) (p = 0.0025). At BE diagnosis, 9.4% had neoplasms: LGD (n = 65), HGD (n = 16), and EAC (n = 49). Among 1258 non-dysplastic BE (NDBE) patients, 4.6% developed a neoplasm—LGD (n = 35), HGD (n = 8), and EAC (n = 15)—with a median observation-period of 5 years (IQR, 3–7). Overall, 160 cases with neoplasms were diagnosed in this BE cohort; 130 (74%) were present at initial BE diagnosis, and 58 (26%) progressed to neoplasms from NDBE. Conclusions: The ratio of long-segment BE was found to be significantly higher in patients ≥ 60 years. Around 9% of the patients were diagnosed as harboring a neoplasm concomitantly with BE, accounting for approximately 74% of all neoplasms. After a median follow-up of 5 years, about 5% of BE showed dysplastic or malignant progression. Full article
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20 pages, 453 KiB  
Review
Current Role of Artificial Intelligence in the Management of Esophageal Cancer
by Evgenia Mela, Dimitrios Tsapralis, Dimitrios Papaconstantinou, Panagiotis Sakarellos, Chrysovalantis Vergadis, Michail E. Klontzas, Ioannis Rouvelas, Antonios Tzortzakakis and Dimitrios Schizas
J. Clin. Med. 2025, 14(6), 1845; https://doi.org/10.3390/jcm14061845 - 9 Mar 2025
Cited by 2 | Viewed by 1303
Abstract
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 [...] Read more.
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
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30 pages, 2199 KiB  
Review
Molecular Abnormalities and Carcinogenesis in Barrett’s Esophagus: Implications for Cancer Treatment and Prevention
by Thaís Cabral de Melo Viana, Eric Toshiyuki Nakamura, Amanda Park, Kaique Flávio Xavier Cardoso Filardi, Rodrigo Moisés de Almeida Leite, Luiz Fernando Sposito Ribeiro Baltazar, Pedro Luiz Serrano Usón Junior and Francisco Tustumi
Genes 2025, 16(3), 270; https://doi.org/10.3390/genes16030270 - 25 Feb 2025
Cited by 1 | Viewed by 1956
Abstract
Background: Barrett’s esophagus (BE) is described by the transformation of the normal squamous epithelium into metaplastic columnar epithelium, driven by chronic gastroesophageal reflux disease (GERD). BE is a recognized premalignant condition and the main precursor to esophageal adenocarcinoma (EAC). Understanding the molecular mechanisms [...] Read more.
Background: Barrett’s esophagus (BE) is described by the transformation of the normal squamous epithelium into metaplastic columnar epithelium, driven by chronic gastroesophageal reflux disease (GERD). BE is a recognized premalignant condition and the main precursor to esophageal adenocarcinoma (EAC). Understanding the molecular mechanisms underlying BE carcinogenesis is crucial for improving prevention, surveillance, and treatment strategies. Methods: This narrative review examines the molecular abnormalities associated with the progression of BE to EAC. Results: This study highlights inflammatory, genetic, epigenetic, and chromosomal alterations, emphasizing key pathways and biomarkers. BE progression follows a multistep process involving dysplasia and genetic alterations such as TP53 and CDKN2A (p16) mutations, chromosomal instability, and dysregulation of pathways like PI3K/AKT/mTOR. Epigenetic alterations, including aberrant microRNA expression or DNA methylation, further contribute to this progression. These molecular changes are stage-specific, with some alterations occurring early in BE during the transition to high-grade dysplasia or EAC. Innovations in chemoprevention, such as combining proton pump inhibitors and aspirin, and the potential of antireflux surgery to halt disease progression are promising. Incorporating molecular biomarkers into surveillance strategies and advancing precision medicine may enable earlier detection and personalized treatments. Conclusions: BE is the primary preneoplastic condition for EAC. A deeper understanding of its molecular transformation can enhance surveillance protocols, optimize the management of gastroesophageal reflux inflammation, and refine prevention and therapeutic strategies, ultimately contributing to a reduction in the global burden of EAC. Full article
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14 pages, 3341 KiB  
Article
Identification of PGC as a Potential Biomarker for Progression from Barrett’s Esophagus to Esophageal Adenocarcinoma: A Comprehensive Bioinformatic Analysis
by Sajida Qureshi, Waqas Ahmad Abbasi, Muhammad Asif Qureshi, Hira Abdul Jalil and Muhammad Saeed Quraishy
Diagnostics 2024, 14(24), 2863; https://doi.org/10.3390/diagnostics14242863 - 19 Dec 2024
Viewed by 1156
Abstract
Background: Barrett’s esophagus (BE), with metaplastic columnar epithelium in the lower esophagus, predisposes patients to esophageal adenocarcinoma (EAC). Despite extensive research, mechanisms underlying BE progression to EAC remain unclear, and no validated biomarkers are available for clinical use. Progastricsin/Pepsinogen-C (PGC), an aspartic [...] Read more.
Background: Barrett’s esophagus (BE), with metaplastic columnar epithelium in the lower esophagus, predisposes patients to esophageal adenocarcinoma (EAC). Despite extensive research, mechanisms underlying BE progression to EAC remain unclear, and no validated biomarkers are available for clinical use. Progastricsin/Pepsinogen-C (PGC), an aspartic proteinase linked to maintaining normal epithelial morphology, is often absent in advanced gastrointestinal malignancies. This study comprehensively investigates PGC expression across cancers, particularly in esophageal cancer (ESCA), to clarify its role in BE progression to EAC. Methods: We utilized multiple bioinformatic platforms (TIMER, UALCAN, cBioPortal, GEPIA, STRING, Metascape, and GEO database) to assess PGC expression, genomic alterations, and correlations with clinicopathological features, survival, and immune infiltration. Additionally, using the GEO dataset, we compared non-dysplastic Barrett’s esophagus (NDBE) patients with those who progressed to malignancy, identifying differentially expressed genes (DEGs), their interactions, and potential roles in progression. Results: PGC was notably upregulated in various cancers, especially in adjacent normal tissues of ESCA. Genomic amplifications of PGC were linked to improved survival in EAC patients, particularly those with high PGC expression, suggesting a protective role. Moreover, PGC expression positively correlated with favorable immune infiltration, notably B cells and CD8+ T cells. Enrichment analysis of downregulated DEGs revealed significant involvement in key biological processes, specifically in extracellular matrix organization. Among the downregulated DEGs, we identified PGC among the top 10 hub genes, underscoring its role in tissue homeostasis. Conclusions: These findings suggest that PGC could serve as a promising biomarker for predicting the high-risk transformation from BE to EAC, offering new insights into EAC progression and future therapeutic targets. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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10 pages, 1579 KiB  
Article
Real-World Clinical Utility of a Methylated DNA Biomarker Assay on Samples Collected with a Swallowable Capsule-Balloon for Detection of Barrett’s Esophagus (BE)
by Dan Lister, Andy Fine, Shail Maheshwari, Paul S. Bradley, Kimberly Lister, Victoria T. Lee, Brian J. deGuzman, Suman Verma and Lishan Aklog
Medicina 2024, 60(12), 2052; https://doi.org/10.3390/medicina60122052 - 13 Dec 2024
Viewed by 1149
Abstract
Background: Barrett’s Esophagus (BE) is the only known precursor for esophageal adenocarcinoma (EAC). Patients with multiple risk factors for BE/EAC are recommended for screening; however, few eligible patients undergo evaluation by endoscopy. EsoGuard® (EG) is a commercially available biomarker assay used to [...] Read more.
Background: Barrett’s Esophagus (BE) is the only known precursor for esophageal adenocarcinoma (EAC). Patients with multiple risk factors for BE/EAC are recommended for screening; however, few eligible patients undergo evaluation by endoscopy. EsoGuard® (EG) is a commercially available biomarker assay used to analyze esophageal cells collected non-endoscopically with EsoCheck® (EC) for the qualitative detection of BE/EAC. This study evaluates the real-world clinical utility of EG on cells collected with EC in patients defined by U.S. gastroenterology societies to be at-risk for BE and EAC. Methods: This multi-center, observational CLinical Utility of EsoGuard (CLUE) study enrolled screening-eligible patients as defined by the American College of Gastroenterology (ACG) and the American Gastroenterological Association (AGA). Clinical utility was evaluated by the provider decision impact of EG and additionally by assessing patient compliance outcomes with recommended follow-up testing. Results: There were 551 patients enrolled, with a mean age of 62.0 ± 12.4 years and 56.1% (309/551) meeting ACG guideline criteria for BE screening. EC cell collection was successful in 97.1% (535/551), among which the EG positivity rate was 27.3% (n = 146). The provider decision impact was high, with 100% of EG-positive patients being referred for esophagogastroduodenoscopy (EGD), while 98% of EG negative patients were not referred. Among the EG-positive patients, the overall compliance with follow-up EGD was 85.4%. Conclusions: Combining EC non-endoscopic esophageal cell collection with the EG biomarker assay is effective in guiding provider decision-making for the detection of BE and EAC. Patients with positive EG results demonstrate high compliance with recommended follow-up EGD. Full article
(This article belongs to the Special Issue Gastroesophageal Reflux Disease and Esophageal Motility Disorders)
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16 pages, 1094 KiB  
Article
Prevalence of Abnormalities at Tandem Endoscopy in Patients Referred for Colorectal Cancer Screening/Surveillance Colonoscopy
by George Triadafilopoulos
Cancers 2024, 16(23), 3998; https://doi.org/10.3390/cancers16233998 - 29 Nov 2024
Cited by 1 | Viewed by 1233
Abstract
Introduction: Performing a tandem endoscopy and colonoscopy in selected individuals has advantages, such as the early detection of benign and/or precancerous foregut diseases; it is efficient, and it may allow added therapies. It may also have disadvantages, such as generating anxiety from false-positive [...] Read more.
Introduction: Performing a tandem endoscopy and colonoscopy in selected individuals has advantages, such as the early detection of benign and/or precancerous foregut diseases; it is efficient, and it may allow added therapies. It may also have disadvantages, such as generating anxiety from false-positive screening, possible harm from further testing, and unproven cost-effectiveness. Aims: We aimed to examine the prevalence of foregut endoscopic and histologic abnormalities in subjects referred for screening/surveillance colonoscopy who also underwent a tandem endoscopy. We wanted to (1) assess implications for cancer detection, intervention, and surveillance of precancerous foregut abnormalities, (2) identify benign foregut lesions, and (3) generate data on the utilities of this tandem approach. Patients and Methods: A retrospective cohort study of consecutive subjects referred for screening or surveillance colonoscopy who also underwent an endoscopy. Based on national screening guidelines, responses to prompting questions, personal or family history, or other risk factors, subjects were assigned to tandem endoscopy with biopsies (modified Seattle and Sydney protocols), under one anesthesia. Results: Of the 1004 patients referred for colonoscopy, 317 (32%) underwent tandem endoscopy. There were 214 women and 103 men. There were 237 Whites, 16 Asians, 40 Blacks, and 24 Hispanics. Median age was 59 (range 19–85). At endoscopy, we identified actionable benign (45%) peptic, inflammatory, and H. pylori-related abnormalities, and premalignant findings (i.e., intestinal metaplasia, 27%, dysplasia, 2%, and cancer 0.9%), comparable to the premalignant (40.3%) and malignant (0.6%) colonoscopy yield. Conclusions: When implemented based on national screening guidelines, tandem EGD and colonoscopy combines Barrett’s esophagus and gastric cancer screening in one examination, and it has a high yield in a diverse US population. Full article
(This article belongs to the Collection Oncology: State-of-the-Art Research in the USA)
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10 pages, 893 KiB  
Hypothesis
Differences in Gender and Overall Survival for Temperature-Sensitive TP53 Mutations in Gastroesophageal Cancer
by Danial H. Shaikh, Margaret Park, Jiandong Chen, Jeffrey Huang, Mark S. Friedman, Aamir N. Dam, Anjuli K. Luthra, Saraswathi Cappelle, Luis R. Pena, Jennifer B. Permuth and Shaffer R. S. Mok
Medicina 2024, 60(11), 1901; https://doi.org/10.3390/medicina60111901 - 20 Nov 2024
Viewed by 1330
Abstract
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 [...] Read more.
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
(This article belongs to the Section Oncology)
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16 pages, 916 KiB  
Review
The Esophageal Microbiota in Esophageal Health and Disease
by Erica Bonazzi, Greta Lorenzon, Daria Maniero, Caterina De Barba, Luisa Bertin, Brigida Barberio, Renato Salvador, Michele Valmasoni, Fabiana Zingone, Matteo Ghisa and Edoardo Vincenzo Savarino
Gastroenterol. Insights 2024, 15(4), 998-1013; https://doi.org/10.3390/gastroent15040069 - 20 Nov 2024
Cited by 2 | Viewed by 2644
Abstract
The esophagus, traditionally viewed as a sterile conduit, is now recognized as a dynamic habitat for diverse microbial communities. The emerging evidence suggests that the esophageal microbiota plays an important role in maintaining esophageal health and contributing to disease. The aim of this [...] Read more.
The esophagus, traditionally viewed as a sterile conduit, is now recognized as a dynamic habitat for diverse microbial communities. The emerging evidence suggests that the esophageal microbiota plays an important role in maintaining esophageal health and contributing to disease. The aim of this systematic review was to synthesize the current knowledge on the esophageal microbiota composition, its variation between healthy individuals and those with esophageal diseases, and the potential mechanisms through which these microorganisms influence esophageal pathology. A systematic literature search was conducted using multiple databases, including PubMed, Scopus, and Web of Science, to identify relevant studies published up to July 2024. The inclusion criteria encompassed original research articles that used molecular techniques to characterize the esophageal microbiota in human subjects, comparing healthy individuals with patients affected by esophageal conditions such as gastroesophageal reflux disease (GERD), Barrett’s esophagus, eosinophilic esophagitis, and esophageal cancer. The primary outcomes were the composition and diversity of the esophageal microbiota, and the secondary outcomes included the correlations between microbial profiles and disease states. The esophageal microbiota of healthy individuals was dominated by Gram-positive bacteria, particularly Streptococcus. Conversely, the esophageal microbiota is considerably altered in disease states, with decreased microbial diversity and specific microbial signatures associated with these conditions, which may serve as biomarkers for disease progression and as targets for therapeutic intervention. However, the heterogeneous study designs, populations, and analytical methods underscore the need for standardized approaches in future research. Understanding the esophageal microbiota’s role in health and disease could guide microbiota-based diagnostics and treatments, offering novel avenues for managing esophageal conditions. Full article
(This article belongs to the Special Issue Recent Advances in the Management of Gastrointestinal Disorders)
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