Search Results (153)

Esophageal cancer (EC), including esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), remains a highly lethal disease because of its late diagnosis, significant biological heterogeneity, and frequent resistance to therapy. Growing evidence indicates that microRNAs (miRNAs) are key posttranscriptional regulators involved in tumor initiation, progression, metastasis, and response to treatment. This review provides a comprehensive and updated overview of miRNA dysregulation in both ESCC and EAC, with a specific focus on its emerging clinical relevance in early detection, prognostic assessment, and prediction of therapeutic response. Multiple tissue-based and circulating miRNA signatures, some capable of distinguishing between Barrett’s esophagus (BE), dysplasia, and EAC, demonstrate promising diagnostic performance. In parallel, several miRNAs, including miR-21, miR-23a, miR-455-3p, and miR-196b, have been consistently associated with chemoresistance and radioresistance. Moreover, distinct miRNA expression patterns are correlated with tumor aggressiveness, metastatic potential, and the risk of recurrence, supporting their integration with conventional histopathological and molecular parameters for improved patient stratification. Overall, miRNAs represent a powerful class of biomarkers and potential therapeutic targets in EC, with increasing translational relevance in precision oncology. Full article

Background/Objectives: Barrett’s esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC), and neoadjuvant chemoradiation therapy (NCRT) is commonly used in the treatment of EAC. However, the impact of NCRT on non-tumorous BE and dysplasia is poorly understood. Our study aims to evaluate the effects of NCRT on BE segment length and dysplasia in patients undergoing esophagectomy for EAC. Methods: This multicenter, retrospective cohort study includes EAC patients who underwent esophagectomy with or without NCRT between 2014 and 2020. Patients with histologically confirmed BE and dysplasia (low- or high-grade) were analyzed. Preoperative and postoperative pathology were compared to assess BE regression, dysplastic changes, and segment length. Statistical analyses included chi-square and t-tests, with p < 0.05 considered significant. Results: Of 101 patients who were diagnosed with EAC, 28 patients were found to have BE, with 18 receiving NCRT in addition to surgery and 10 undergoing surgery alone. The NCRT group showed significantly higher BE regression than the control group (77.8% versus 10%, p < 0.001). Regression of dysplasia occurred in 66.7% of the NCRT group versus 20% of the control group (p = 0.079) and residual dysplasia was lower in the NCRT group (33.3%) compared to the control group (80%) (p = 0.018). Conclusions: NCRT significantly reduces BE and dysplasia, suggesting it may improve surgical outcomes by minimizing residual disease. These findings support the potential of NCRT to enhance surgical precision in EAC treatment, though further research is needed to explore underlying mechanisms and refine treatment strategies. Full article

Cryotherapy involves flash freezing of tissue and removing unwanted tissue. Mechanism of injury is causing cell membrane rupture by rapid multiple freeze–thaw cycles, while reserving tissue architecture and the collagen matrix. This promotes favorable wound healing. In recent years, it has gained increasing attention as a treatment option for upper gastrointestinal diseases (Barrett’s Esophagus and early cancer). Currently, two FDA-approved delivery methods are available in the GI tract: Cryoballoon and spray cryotherapy, which will be discussed. In this review, we also propose to examine the expanding role of cryotherapy in gastrointestinal practice, drawing from both clinical studies and illustrative vignettes. In addition, we will highlight its established role in eradicating Barrett’s with low and high-grade dysplasia and compare its outcomes and safety profile with radiofrequency ablation (RFA). We will also discuss the application and safety of spray cryotherapy in the palliation of malignant esophageal strictures when compared with Esophageal stent placement. Cryotherapy may have immunological potential, and it may shrink both primary and metastatic diseases. Ongoing research in this field of Cryo-immunology will be highlighted. Beyond esophageal neoplasia, cryotherapy is increasingly utilized in other upper gastrointestinal precancerous conditions. Through this synthesis, our goal is to provide a timely and comprehensive overview of advancements in cryotherapy and its potential to reshape novel therapeutic approaches in upper gastrointestinal cancers. Finally, we highlight the evolution of a novel platform using nitrous oxide delivered by a handheld device, a contact balloon, and a small replaceable cartridge. This approach may make delivery of cryogen application favorable and a first-line approach in the management of Barrett’s esophagus and early cancer. In addition, Cryoballoon therapy for dysphagia palliation for malignant esophageal strictures may become a preferred approach as more data evolves. Full article

Background and Clinical Significance: Cryotherapy, particularly with the CryoBalloon Focal Ablation System (CbFAS), has emerged as a minimally invasive modality delivering targeted ablation through liquid nitrous oxide. While its role in treating Barrett’s esophagus and dysplasia is well established, its application in early esophageal adenocarcinoma (EAC) salvage treatment remains limited. Case Presentation: We report the case of an 84-year-old male with Barrett’s esophagus and multiple comorbidities who underwent endoscopic submucosal dissection (ESD) for a 3 cm esophageal adenocarcinoma (pT1bN0M0). Histology revealed deep submucosal invasion, perivascular infiltration, and positive margins, rendering the resection non-curative. Given surgical ineligibility, the patient underwent cryoballoon ablation six months later for recurrent intramucosal carcinoma proximal to the ESD scar. At three months, surveillance endoscopy showed residual Barrett’s esophagus with low-grade dysplasia. Conclusions: This case highlights the feasibility and safety of cryoballoon ablation as salvage therapy after non-curative ESD in inoperable EAC. To our knowledge, this represents the first report of salvage CbFAS in T1bN0M0 EAC, underscoring the need for further studies to define its role in the multimodal management of EAC. Full article

Esophageal cancer (EC) is one of the most aggressive cancers of the digestive system, with two main subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Over four decades, the frequencies of EAC and Barrett’s esophagus (BE), the known precursor lesion for EAC, have sharply increased in North America and Europe. This is mainly due to lifestyle and risk factors such as gastroesophageal reflux disease (GERD), obesity, and smoking. BE development to EAC involves numerous molecular modifications, including genetic and epigenetic alterations. Epigenetic changes, such as aberrant DNA methylation, play a critical role in the pathogenesis and progression of BE. This review discusses how non-genetic risk factors contribute to DNA methylation changes driving the transformation from BE to EAC, providing insights into the potential of developing methylation-based biomarkers for early diagnosis, risk stratification, and therapeutic intervention. Full article

Esophageal cancer (EC) is a highly aggressive gastrointestinal malignancy, with a notable increase in incidence over recent decades, representing a significant global health burden. The main histological subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), with the former being closely associated with gastroesophageal reflux disease, Barrett’s esophagus, and obesity, and its incidence continues to increase in Western populations. The rising incidence of EC, combined with poor survival rates, underscores the need for new therapeutic approaches. A deeper understanding of the molecular basis of this prevalent malignancy may open new avenues for optimal therapeutic strategies, with immunotherapy now central in several clinical trials. Understanding the interplay between the tumor microenvironment (TME) and disease progression is pivotal for managing this malignancy, which remains highly challenging. This review highlights the role of the TME in EAC progression and drug resistance, and recent therapeutic advances. Full article

Background and Clinical Significance: Barrett’s esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Accurately predicting which patients with BE are at the highest risk of progressing to EAC is a significant clinical challenge. This article discusses how the tissue systems pathology test (TSP-9, TissueCypher) can help guide risk-aligned care for patients with BE. TSP-9 is an AI-driven prognostic test that stratifies patients with BE for risk of progression to high-grade dysplasia (HGD)/EAC. Case Report Presentation: Three clinically low-risk patients had esophageal biopsies tested by TSP-9. The real-world utility of TSP-9 is demonstrated through a brief discussion of how the test was utilized to assess each patient’s personalized risk of BE progression to HGD/EAC and inform risk-aligned care. Conclusions: The use of validated AI-powered tools such as TSP-9 is poised to become standard practice in gastroenterology clinical settings and will help improve health outcomes for patients with BE to prevent EAC-related mortality. Full article

Optical imaging technologies expand gastrointestinal endoscopy beyond white-light endoscopy (WLE), improving visualization of mucosal, vascular, and subsurface features. They are applied to the detection of neoplastic and premalignant lesions, inflammatory diseases, and small bowel and pancreatic disorders, though their validation and readiness for routine practice vary. This review critically evaluates both guideline-endorsed and investigational optical imaging techniques across major gastrointestinal indications, highlighting diagnostic performance, level of validation, current guideline recommendations, and practical challenges to adoption. In Barrett’s esophagus, narrow-band imaging (NBI) is guideline-endorsed, while acetic acid chromoendoscopy is validated in expert centers. For gastric intestinal metaplasia and early gastric cancer, magnifying NBI achieves diagnostic accuracies exceeding 90% and is guideline-recommended, with acetic acid chromoendoscopy aiding in margin delineation. In inflammatory bowel disease, dye-spray chromoendoscopy is the reference standard for dysplasia surveillance, with virtual methods such as NBI, FICE, and i-SCAN serving as practical alternatives when dye application is not feasible. In the colorectum, NBI supports validated optical diagnosis strategies (resect-and-discard, diagnose-and-leave), while dye-based chromoendoscopy improves detection of flat and serrated lesions. Capsule endoscopy remains the standard for small bowel evaluation of bleeding, Crohn’s disease, and tumors, with virtual enhancement, intelligent chromo capsule endoscopy, and AI-assisted interpretation emerging as promising adjuncts. Pancreaticobiliary applications of optical imaging are also advancing, though current evidence is still preliminary. Investigational modalities including confocal laser endomicroscopy, optical coherence tomography, autofluorescence, Raman spectroscopy, and fluorescence molecular imaging show potential but remain largely restricted to research or expert settings. Guideline-backed modalities such as NBI and dye-based chromoendoscopy are established for clinical practice and supported by robust evidence, whereas advanced techniques remain investigational. Future directions will rely on broader validation, integration of artificial intelligence, and adoption of molecularly targeted probes and next-generation capsule technologies, which together may enhance accuracy, efficiency, and standardization in gastrointestinal endoscopy. Full article

Background and Objectives: Barrett’s Esophagus (BE) is a precursor to esophageal adenocarcinoma, and early detection is essential to reduce cancer risk. This study aims to develop a YOLO-based ensemble framework to improve the automated detection of BE-associated mucosal lesions on endoscopic images. Methods: A dataset of 3620 annotated endoscopic images was collected from 132 patients. Five YOLO variants, YOLOv5, YOLOv9, YOLOv10, YOLOv11, and YOLOv12, were selected based on their architectural diversity and detection capabilities. Each model was trained individually, and their outputs were integrated using a Non-Maximum Suppression (NMS)-based ensemble strategy. Multiple ensemble configurations were evaluated to assess the impact of fusion depth on detection performance. Results: The ensemble models consistently outperformed individual YOLO variants in recall, the primary evaluation metric. The entire five-model ensemble achieved the highest recall (0.974), significantly reducing missed lesion detections. Statistical analysis using McNemar’s test and bootstrap confidence intervals confirmed the superiority in most comparisons. Conclusions: The proposed YOLO ensemble framework demonstrates enhanced sensitivity and robustness in detecting BE lesions. Its integration into clinical workflows can improve early diagnosis and reduce diagnostic workload, offering a promising tool for computer-aided screening in gastroenterology. Full article

Background/Objectives: Esophageal and esophagogastric junction adenocarcinoma (EADC-EGJA), which mainly develops from Barrett’s esophagus (BE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD), has a poor prognosis and several unmet clinical needs, among which is the detection of minimal residual disease (MRD) after endoscopic/surgical resection. Long interspersed nuclear element-1 (LINE-1), a surrogate marker of global methylation, is considered an emerging biomarker for MRD monitoring. The aim of this study was to determine, by LINE-1 methylation analysis, at which carcinogenesis step global methylation is affected and whether this biomarker could be followed in longitudinal to monitor the disease behavior post-surgery. Methods: Cell-free DNA of 90 patients with non-dysplastic Barrett’s esophagus (NDBE), HGD/early EADC-EGJA, or locally advanced/advanced EADC-EGJA were analyzed for LINE-1 methylation, by Methylation-Sensitive Restriction Enzyme droplet digital PCR (MSRE-ddPCR). Twenty-six patients were longitudinally studied by repetitive blood sampling. Results: Global hypomethylation increased during carcinogenesis, with significant difference between locally advanced/advanced EADC-EGJA and NDBE patients (p = 0.028). Longitudinal cases confirmed the rareness of hypomethylation in NDBE cases. The majority of HGD/early EADC-EGJA and locally advanced/advanced EADC-EGJA patients showed methylation changes after resection according to clinical status. Conclusions: This study suggests that global hypomethylation occurs just prior to cancer invasiveness and that it is a promising biomarker to monitor MRD. Full article

Helicobacter pylori (Hp), a widespread gastric pathogen, has long been studied for its role in upper gastrointestinal disorders. While its involvement in gastritis, peptic ulcer disease, and gastric cancer is well established, its impact on esophageal diseases remains an area of ongoing investigation. Nevertheless, some data indicate that Hp may be involved in the pathogenesis of gastroesophageal reflux disease–Barrett’s esophagus–esophageal adenocarcinoma sequence. Similarly, the Hp-related mast cell activation—an essential immunological event—may also play a crucial role in the progression from gastroesophageal reflux disease to Barrett’s esophagus and esophageal adenocarcinoma. The underlying mechanisms include immune modulation, cytokine cascades, and microbial interactions that collectively shape the esophageal microenvironment. This review provides an in-depth analysis of these pathways, highlighting the potential role of Hp-induced, mast cell-driven inflammation in esophageal disease progression and discussing emerging therapeutic strategies. Full article

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

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

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

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