Search Results (21)

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

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

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

Barrett’s esophagus (BE) is a known precursor to esophageal adenocarcinoma (EAC). Guidelines recommend BE screening in populations with multiple risk factors, for which non-endoscopic esophageal cell collection with biomarker testing is considered as an acceptable alternative to esophagogastroduodenoscopy (EGD). The aim of this study was to evaluate analytical performance characteristics of EsoGuard^® (EG), a DNA methylation biomarker assay, as a laboratory-developed test (LDT) in esophageal samples collected with the swallowable EsoCheck^® (EC) device. EG is a next-generation sequencing (NGS) assay that evaluates methylated vimentin (VIM) and cyclin A1 (CCNA1), clinically validated biomarkers for the detection of BE and EAC. The studies were conducted according to standards of College of American Pathology (CAP), Clinical Laboratory Improvement Amendments (CLIA), and New York (NY) state requirements for the analytical validation of molecular assays. Comparison to Sanger sequencing showed that EG was 100% accurate at all 31 CpG sites evaluated by the assay. The analytical sensitivity, specificity, and accuracy of the assay were 89%, 100%, and 96%, respectively. Intra- and inter-assay precision was 100%. The limit of detection (LOD) was 1 in 400 methylated cells, and the reference range was 84%. In summary, EsoGuard demonstrates high analytical accuracy, repeatability, and reproducibility in samples collected using the EsoCheck device. Full article

Gastroesophageal reflux disease (GERD) is one of the most common diseases that occurs secondary to failure of the antireflux barrier system, resulting in the frequent and abnormal reflux of gastric contents to the esophagus. GERD is diagnosed in routine clinical practice based on the classic symptoms of heartburn and regurgitation. However, a subset of patients with atypical symptoms can pose challenges in diagnosing GERD. An esophagogastroduodenoscopy (EGD) is the most common initial diagnostic test used in the assessment for GERD, although half of these patients will not have any positive endoscopic findings suggestive of GERD. The advanced endoscopic techniques have improved the diagnostic yield of GERD diagnosis and its complications, such as Barrett’s esophagus and early esophageal adenocarcinoma. These newer endoscopic tools can better detect subtle irregularities in the mucosa and vascular structures. The management options for GERD include lifestyle modifications, pharmacological therapy, and endoscopic and surgical interventions. The latest addition to the armamentarium is the minimally invasive endoscopic interventions in carefully selected patients, including the electrical stimulation of the LES, Antireflux mucosectomy, Radiofrequency therapy, Transoral Incisionless Fundoplication, Endoscopic Full-Thickness plication (GERDx™), and suturing devices. With the emergence of these advanced endoscopic techniques, it is crucial to understand their selection criteria, advantages, and disadvantages. Full article

Esophageal carcinoma is the sixth-leading cause of cancer death worldwide. A precursor to esophageal adenocarcinoma (EAC) is Barrett’s Esophagus (BE). Early-stage diagnosis and treatment of esophageal neoplasia (Barrett’s with high-grade dysplasia/intramucosal cancer) increase the five-year survival rate from 10% to 98%. BE is a global challenge; however, current endoscopes for early BE detection are costly and require extensive infrastructure for patient examination and sedation. We describe the design and evaluation of the first prototype of ScanCap, a high-resolution optical endoscopy system with a reusable, low-cost tethered capsule, designed to provide high-definition, blue-green illumination imaging for the early detection of BE in unsedated patients. The tethered capsule (12.8 mm diameter, 35.5 mm length) contains a color camera and rotating mirror and is designed to be swallowed; images are collected as the capsule is retracted manually via the tether. The tether provides electrical power and illumination at wavelengths of 415 nm and 565 nm and transmits data from the camera to a tablet. The ScanCap prototype capsule was used to image the oral mucosa in normal volunteers and ex vivo esophageal resections; images were compared to those obtained using an Olympus CV-180 endoscope. Images of superficial capillaries in intact oral mucosa were clearly visible in ScanCap images. Diagnostically relevant features of BE, including irregular Z-lines, distorted mucosa, and dilated vasculature, were clearly visible in ScanCap images of ex vivo esophageal specimens. Full article

Barrett’s esophagus (BE) is a disease entity that is a sequela of chronic gastroesophageal reflux disease that may result in esophageal adenocarcinoma (EAC) due to columnar epithelial dysplasia. The histological degree of dysplasia is the sole biomarker frequently utilized by clinicians. However, the cost of endoscopy and the fact that the degree of dysplasia does not progress in many patients with BE diminish the effectiveness of histological grading as a perfect biomarker. Multiple or more quantitative biomarkers are required by clinicians since early diagnosis is crucial in esophageal adenocancers, which have a high mortality rate. The presence of epigenetic factors in the early stages of this neoplastic transformation holds promise as a predictive biomarker. In this review, current studies on DNA methylations, histone modifications, and noncoding RNAs (miRNAs) that have been discovered during the progression from BE dysplasia to EAC were collated. Full article

Barrett esophagus (BE) is a precursor to a life-threatening esophageal adenocarcinoma (EAC). Surveillance endoscopy with random biopsies is recommended for early intervention against EAC, but its adherence in the clinical setting is poor. Dysplastic lesions with flat architecture and patchy distribution in BE are hardly detected by high-resolution endoscopy, and the surveillance protocol entails issues of time and labor and suboptimal interobserver agreement for diagnosing dysplasia. Therefore, the development of advanced imaging technologies is necessary for Barrett’s surveillance. Recently, non-endoscopic or endoscopic technologies, such as cytosponge, endocytoscopy, confocal laser endomicroscopy, autofluorescence imaging, and optical coherence tomography/volumetric laser endomicroscopy, were developed, but most of them are not clinically available due to the limited view field, expense of the equipment, and significant time for the learning curve. Another strategy is focused on the development of molecular biomarkers, which are also not ready to use. However, a combination of advanced imaging techniques together with specific biomarkers is expected to identify morphological abnormalities and biological disorders at an early stage in the surveillance. Here, we review recent developments in advanced imaging and molecular imaging for Barrett’s neoplasia. Further developments in multiple biomarker panels specific for Barrett’s HGD/EAC include wide-field imaging systems for targeting ‘red flags’, a high-resolution imaging system for optical biopsy, and a computer-aided diagnosis system with artificial intelligence, all of which enable a real-time and accurate diagnosis of dysplastic BE in Barrett’s surveillance and provide information for precision medicine. Full article

Confocal laser endomicroscopy (CLE) is a diagnostic technique that enables real-time microscopic imaging during microscopic examination and evaluation of epithelial structures with 1000-fold magnification. CLE can be used in the diagnosis of various pathologies, in pneumology, and in urology, and it is very widely utilized in gastroenterology, most importantly in the diagnosis of Barrett’s esophagus (BE), esophageal adenocarcinoma (EAC), biliary strictures, and cystic pancreatic lesions. A literature search was made in MEDLINE/PubMed and Google Scholar databases while focusing on diagnostics using CLE of BE and EAC. We then examined randomized and observational studies, systematic reviews, and meta-analyses relating to the utilization of CLE in BE and EAC diagnostics. Here, we discuss whether CLE can be a suitable diagnostic method for surveillance of BE. Even though many studies have proven that CLE increases diagnostic accuracy in detecting neoplastic transformation of BE, CLE is still not used as a standard diagnostic tool in BE surveillance due to a deficiency of scientific evidence. More studies and data are needed if CLE is to find a place as a new technique in BE surveillance. Full article

Despite therapeutical advancements, and in contrast to other malignancies, esophageal adenocarcinoma (EAC) prognosis remains dismal while the incidence has markedly increased worldwide over the past decades. EAC is a malignancy of the distal esophageal squamous epithelium at the squamocolumnar junction with gastric cells expanding into the esophagus. Most EAC patients have a history of Barret’s esophagus (BE), a metaplastic adaption to chronic reflux, initially causing an inflammatory microenvironment. Thus, the immune system is highly involved early on in disease development and progression. Normally, anti-tumor immunity could prevent carcinogenesis but in rare cases BE still progresses over a dysplastic intermediate state to EAC. The inflammatory milieu during the initial esophagitis phase changes to a tolerogenic immune environment in BE, and back to pro-inflammatory conditions in dysplasia and finally to an immune-suppressive tumor microenvironment in EAC. Consequently, there is a huge interest in understanding the underpinnings that lead to the inflammation driven stepwise progression of the disease. Since knowledge about the constellations of the various involved cells and signaling molecules is currently fragmentary, a comprehensive description of these changes is needed, allowing better preventative measures, diagnosis, and novel therapeutic targets. Full article

Esophageal adenocarcinoma is increasing in incidence and is the most common subtype of esophageal cancer in Western societies. The stepwise progression of Barrett´s metaplasia to high-grade dysplasia and invasive adenocarcinoma provides an opportunity for screening and surveillance. There are important unresolved issues, which include (i) refining the definition of the screening population in order to avoid unnecessary invasive diagnostics, (ii) a more precise prediction of the (very heterogeneous) individual progression risk from metaplasia to invasive cancer in order to better tailor surveillance recommendations, (iii) improvement of the quality of endoscopy in order to reduce the high miss rate for early neoplastic lesions, and (iv) support for the diagnosis of tumor infiltration depth in order to guide treatment decisions. Artificial intelligence (AI) systems might be useful as a support to better solve the above-mentioned issues. Full article

Esophageal cancer (EC) is an aggressive malignant disease ranking amongst the leading causes of cancer deaths in the world. The two main histologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have distinct geographic and temporal patterns and risk factor profiles. Despite decades of research, the factors underlying these geo-temporal patterns are still not fully understood. The human microbiome has recently been implicated in various health conditions and disease, and it is possible that the microbiome may play an important role in the etiology of EC. Although studies of the microbiome and EC are still in their early stages, we review our current understanding of the potential links between ESCC, EAC, and bacterial communities in the oral cavity and esophagus. We also provide a summary of the epidemiology of EC and highlight some key challenges and future directions. Full article

Esophageal cancer (EC) is the seventh most common cancer and the sixth cause of cancer death worldwide. Histologically, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) account for up to 90% and 20% of all ECs, respectively. Clinical symptoms such as dysphagia, odynophagia, and bolus impaction occur late in the natural history of the disease, and the diagnosis is often delayed. The prognosis of ESCC and EAC is poor in advanced stages, being survival rates less than 20% at five years. However, when the diagnosis is achieved early, curative treatment is possible, and survival exceeds 80%. For these reasons, mass screening strategies for EC are highly desirable, and several options are currently under investigation. Blood biomarkers offer an inexpensive, non-invasive screening strategy for cancers, and novel technologies have allowed the identification of candidate markers for EC. The esophagus is easily accessible via endoscopy, and endoscopic imaging represents the gold standard for cancer surveillance. However, lesion recognition during endoscopic procedures is hampered by interobserver variability. To fill this gap, artificial intelligence (AI) has recently been explored and provided encouraging results. In this review, we provide a summary of currently available options to achieve early diagnosis of EC, focusing on blood biomarkers, advanced endoscopy, and AI. Full article

Diagnosis of esophageal adenocarcinoma mostly occurs in the context of reflux disease or surveillance of Barrett’s metaplasia. Optimal detection rates are obtained with high definition and virtual or dye chromoendoscopy. Smaller lesions can be treated with endoscopic mucosal resection. Endoscopic submucosal dissection (ESD) is an option for larger lesions. Endoscopic resection is considered curative (i.e., without significant risk of lymph node metastasis) if histopathology confirms en bloc and R0 resection of a well-differentiated (G1/2) tumor without infiltration of lymphatic or blood vessels and the maximal submucosal infiltration depth is 500µm. Ablation of remaining Barrett’s metaplasia is important, to reduce the risk of metachronous cancer. Esophageal squamous cell cancer is associated with different risk factors, and most of the detected lesions are diagnosed during upper gastrointestinal endoscopy for other indications. Virtual high definition and dye chromoendoscopy with Lugol’s solution are used for screening and evaluation. ESD is the preferred resection technique. The criteria for curative resection are similar to Barrett’s cancer, but the maximum infiltration depth must not exceed lamina propria mucosae. Although a submucosal infiltration depth of up to 200 µm carries a substantial risk of lymph node metastasis, ESD combined with adjuvant chemo-radiotherapy gives excellent results. The complication rates of endoscopic resection are low, and the functional outcomes are favorable compared to surgery. Full article

Esophageal adenocarcinoma (EAC), the major histologic type of esophageal cancer (EC) in Western countries, is a disease with a poor prognosis, primarily due to usual diagnosis at an advanced stage. The prevalence of EAC has increased in recent years, both in Western countries and in Asia. Barrett’s esophagus (BE) is a precursor lesion of EAC. Therefore, early detection and proper management of BE and EAC is important to improve prognosis. Here, we systematically summarize current knowledge about the potential utility of extracellular microRNAs (miRNAs), which are thought to be non-invasive biomarkers for many diseases, for these purposes. A search of the PubMed and Embase databases identified 22 papers about extracellular miRNAs that have potential utility for management of EAC. Among them, 19 were EAC-related and ten were BE-related; some of these dealt with both conditions. The articles included studies reporting diagnosis, prognosis, and treatment responses. Multiple papers report dysregulation of miR-194-5p in BE and miR-21-5p, -25-3p, and -93-5p in EAC. Although it will take time to utilize these miRNAs in clinical practice, they are likely to be useful non-invasive markers in the future. Full article