Search Results (158)

Barrett’s esophagus (BE), the intestinal metaplasia arising from chronic gastroesophageal reflux disease, is the principal identifiable precursor of esophageal adenocarcinoma (EAC), whose incidence rose from 0.4 to 2.8/100,000 person-years between 1975 and 2017 and whose prognosis, once symptomatic, remains poor. Because outcomes depend on intercepting the metaplasia–dysplasia–carcinoma sequence, diagnostic accuracy is decisive. White-light endoscopy with Seattle-protocol biopsy remains the reference standard, yet it is constrained by the following three interrelated weaknesses: sampling error, as random forceps biopsies interrogate only about 3.5% of the Barrett’s mucosa; poor reproducibility of dysplasia grading, with interobserver agreement of only κ 0.24–0.27 for the pivotal distinction of low-grade dysplasia; and a substantial burden of missed disease, with roughly one-quarter of EACs diagnosed within a year of an index endoscopy reported as nondysplastic. This review synthesizes the technologies converging to address these gaps. Advanced imaging, encompassing high-definition endoscopy, narrow-band imaging, acetic acid chromoendoscopy, and the optical-biopsy platforms confocal laser and volumetric laser endomicroscopy, raises dysplasia yield by approximately 34% over standard white-light examination. Image-enhanced endoscopy improves targeted detection while remaining complementary to structured biopsy sampling. Molecular, genetic, and epigenetic biomarkers, notably DNA-content abnormalities, p53 immunohistochemistry, and multi-gene methylation panels, add an objective read on progression risk. Their pairing with non-endoscopic sampling, including Cytosponge-TFF3, capsule endoscopy, exhaled volatile organic compounds, and circulating microRNA liquid biopsy, is reshaping screening at population scale, while artificial intelligence standardizes interpretation and narrows the expert–nonexpert gap. Together these advances point toward a risk-stratified, multimodal paradigm, though prospective validation and cost-effectiveness evidence remain prerequisites for guideline adoption. Full article

Gastroesophageal reflux disease (GERD) is a common chronic disorder of the upper gastrointestinal tract, traditionally explained by an acid-centric model in which gastric acid causes mucosal injury and symptoms. Proton pump inhibitors (PPIs) are the mainstay of therapy and effectively control symptoms in many patients. However, up to 50% of individuals remain symptomatic despite adequate acid suppression, suggesting that GERD is a multifactorial condition involving anti-reflux barrier dysfunction, impaired mucosal defense, immune activation, and alterations in the esophageal microbiota. This study is a narrative review aimed at evaluating current evidence on the interactions between acid suppression, esophageal microbial ecology, and host–microbe interactions in GERD, and at exploring the potential role of microbiota-targeted therapeutic strategies. The literature search was conducted using electronic databases (e.g., PubMed and Scopus), without formal time restrictions, prioritizing recent and clinically relevant studies. Evidence was qualitatively synthesized to provide an integrated overview. Recent studies suggest that the esophagus hosts a microbial ecosystem that may contribute to mucosal homeostasis. In GERD and Barrett’s esophagus, several studies report a shift toward Gram-negative anaerobic bacteria with potential pro-inflammatory activity. Long-term PPI therapy has been associated with increased gastric pH and changes in gastrointestinal microbiota composition, including a relative increase in taxa such as Streptococcus and Veillonella, and a reduction in short-chain fatty acid–producing bacteria. These alterations may be linked to dysbiosis and a possible increase in susceptibility to certain infections, although causality remains to be fully established. The main limitations of this review include its narrative design, the absence of systematic study selection, and the heterogeneity of the available evidence. Understanding the impact of acid suppression on microbial ecology may support the development of more integrated and personalized therapeutic strategies. Full article

Transoral endoscopic therapies in gastro-esophageal reflux disease (GERD) are increasingly performed in patients who do not respond to medical therapy or are not suitable for or willing to undergo long-term PPI therapy or surgery. Currently available effective techniques include reconstruction of the gastro-esophageal valve by transoral incisionless fundoplication (TIF) and tightening of the gastro-esophageal junction through scarring, obtained by mucosal resection or ablation. TIF may be accomplished by an EsophyX 2.0/Z, MUSE, or GERD-X device. An iatrogenic stricture of the cardia may be obtained using a procedure called anti-reflux mucosectomy (ARMS), which includes several technical variants, or through mucosal ablation (ARMA). TIF using EsophyX 2.0 has strong evidence of efficacy in patients with small hiatal hernias, irrespective of hernia reducibility, who experience high-volume reflux episodes and troublesome regurgitation despite PPI therapy. MUSE can be performed only in the presence of a spontaneously reducing hiatal hernia and is probably more effective than EsophyX in maintaining the reduced hernia over time. However, MUSE is no longer available in Western countries. GERD-X shows promising results but needs further confirmation of its efficacy over the long term. ARMS and ARMA are not indicated in the presence of hiatal hernias but have shown promising results in the short term and are less expensive than TIF. Appropriate patient selection and the possibility of proposing a tailored approach to different types of patients and clinical/anatomical conditions result in favorable outcomes in most GERD patients, especially considering their quality of life and independence from PPIs. In the last several years, transoral endoscopic therapies have been proposed, along with concomitant laparoscopic repair for large hiatal hernias (cTIF), for GERD occurring after esophageal peroral endoscopic myotomy (E-POEM), in obese patients before or after bariatric surgery, and in patients with Barrett’s esophagus. Full article

Confocal laser endomicroscopy (CLE) is an innovative diagnostic modality that facilitates real-time in vivo optical biopsies of various tissues within luminal and ductal structures. Since its introduction in 2004, the application of this tool has broadened from diagnostic purposes to encompass management and prognostic evaluation in fields such as gastroenterology, neurosurgery, urology, and dermatology. This comprehensive review examines the current applications of endomicroscopy in Barrett’s esophagus (BE), inflammatory bowel disease (IBD), and colorectal lesions. Evidence from the literature suggests that CLE offers a potential solution to the diagnostic limitations associated with white-light endoscopy and histology. With a diagnostic accuracy nearly equivalent to that of histology, CLE is emerging as a promising tool to mitigate the delays related to awaiting histology results for clinical and therapeutic decision-making. However, its use is mainly as a complementary diagnostic method rather than an alternative to histopathology or other ancillary studies. Nevertheless, its widespread adoption remains limited, and further research is necessary to ascertain its overall benefits and cost implications of integrating it into patient care. Full article

Mucins are high-molecular-weight glycoproteins that form the main structural component of the mucus covering epithelial surfaces in the gastrointestinal, respiratory, and urogenital tracts. They support epithelial integrity by protecting against microbial invasion, dehydration, and mechanical or chemical insults, while facilitating the transit of luminal contents. Beyond their structural function, mucins play key roles in molecular recognition. Their extensive glycosylation enables interactions with a wide range of molecules and allows the discrimination between pathogenic and commensal microorganisms at mucosal surfaces. Mucins help maintain mucosal homeostasis by preventing pathogen adhesion and colonization, while simultaneously providing nutrients to commensal species, supporting their stability, and maintaining spatial segregation from epithelial surfaces. Aberrant expression of mucin subtypes or alterations in their glycosylation patterns are associated with numerous diseases, including a wide spectrum of cancers and inflammatory disorders. The immunological relevance of the esophageal mucosa has only recently been recognized. Advances in the study of the esophageal mucosa-associated immune surveillance system and its interactions with structural components of this organ’s surface, including mucins, have shed light on unique pathological processes in the esophagus, such as Barrett’s esophagus, gastroesophageal reflux disease, and eosinophilic esophagitis. This review focuses on the role of esophageal mucins in inflammation, compiling current evidence to provide an integrated overview of mucin-driven inflammatory mechanisms. Full article

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