Endoscopic Surveillance for Premalignant Esophageal Lesions: A Community-Based Multicenter, Prospective Cohort Study.

BACKGROUND & AIMS: Mild and moderate dysplasia are major premalignant lesions of esophageal squamous cell carcinoma (ESCC); however, evidence of the progression risk in patients with these conditions is extremely limited. We aimed to assess the incidence and risk factors for advanced neoplasia in patients with mild-moderate dysplasia. METHODS: This prospective cohort study included patients with mild-moderate dysplasia from 9 regions in rural China. These patients were identified from a community-based ESCC screening program conducted between 2010 and 2016 and were offered endoscopic surveillance until December 2021. We estimated the incidence of advanced esophageal neoplasia, including severe dysplasia, carcinoma in situ, or ESCC, and identified potential risk factors using the Cox regression model. RESULTS: The 1183 patients with mild-moderate dysplasia were followed up over a period of 6.95 years. During follow-up evaluation, 88 patients progressed to advanced neoplasia (7.44%), with an incidence rate of 10.44 per 1000 person-years. The median interval from the progression of mild-moderate dysplasia to advanced neoplasia was 2.39 years (interquartile range, 1.58-4.32 y). A total of 74.47% of patients with mild-moderate dysplasia experienced regression to nondysplasia, and 18.09% showed no lesion progression. Patients with mild-moderate dysplasia who had a family history of esophageal cancer and were age 55 years and older showed 97% higher advanced neoplasia yields than all patients with mild-moderate dysplasia. CONCLUSIONS: In a country with a high incidence of ESCC, patients with mild-moderate dysplasia showed an overall risk of advanced neoplasia progression of 1.04% per year. Patients with mild-moderate dysplasia would be recommended for endoscopic surveillance during the first 2 to 3 years.

Characteristics of the esophageal microbiome in patients with achalasia and its changes before and after peroral endoscopic myotomy: A pilot study.

BACKGROUND AND AIM: Achalasia often presents with chronic food stasis and fermentation in the esophageal lumen, which may lead to alterations of the esophageal microbiome, with associated mucosal inflammation and dysplastic changes. The study aims to evaluate the characteristics of the esophageal microbiome in achalasia and changes of the esophageal microbiome before and after peroral endoscopic myotomy (POEM). METHODS: This is a prospective case-control study. This study enrolled patients with achalasia and asymptomatic subjects as control group. Endoscopic brushing for esophageal microbiome collection was performed in all subjects, with additional follow-up endoscopy and brushing 3 months after POEM in achalasia patients. The composition of the esophageal microbiome was determined and compared between (1) achalasia patients and asymptomatic controls and (2) achalasia patients before and after POEM. RESULTS: Thirty-one achalasia patients (mean age 53.5 ± 16.2 years; male 45.2%) and 15 controls were analyzed. We observed a distinct esophageal microbial community structure in achalasia patients, with increased Firmicutes and decreased Proteobacteria when compared with the control group at the phylum level. The discriminating enriched genera in achalasia patients were Lactobacillus, followed by Megasphaera and Bacteroides, and the amount of Lactobacillus was associated with the severity of achalasia. Twenty patients were re-examined after POEM, and a high prevalence of erosive esophagitis (55%) was noted, alongside an increase in genus Neisseria and decrease in Lactobacillus and Bacteroides. CONCLUSIONS: The altered esophageal microenvironment in achalasia leads to dysbiosis with a high abundance of genus Lactobacillus. Increased Neisseria and decreased Lactobacillus were observed after POEM. The long-term effect of microbial changes warrants further study.

Risk factors for esophageal iodine-unstained lesions and changing trends among Japanese alcohol-dependent men (2003-2018).

Globally, a decreasing incidence of male esophageal squamous cell carcinoma (ESCC) has been observed in recent decades. We evaluated the determinants of esophageal distinct iodine-unstained lesions (DIULs), high-cancer-risk lesions and ESCC, among 3858 Japanese alcohol-dependent men (40-79 years) who underwent chromoendoscopic screening between 2003 and 2018. The initial screening detected DIULs ≥ 5 mm in 541 patients (dysplasia in 319 and SCC in 129) and multiple DIULs in 640. The detection rates for DIULs and chronic atrophic gastritis (CAG), pack-years, and the mean corpuscular volume (MCV) decreased over the course of the study period, while the detection of hiatal hernia and/or columnar-lined esophagus (HH/CLE) and the carriers of inactive heterozygous aldehyde dehydrogenase-2 (ALDH2, rs671) increased. Multiple logistic regression analyses showed that an older age, larger number of pack-years, smaller body mass index, larger MCV, presence of a slow-metabolizing alcohol dehydrogenase-1B genotype (rs1229984), presence of an inactive heterozygous ALDH2 genotype, and more advanced degree of CAG increased the odds ratios (ORs) for DIULs, while the 2008-2013 and 2014-2018 screening periods had lower ORs for DIULs than the 2003-2007 screening period. The presence of HH/CLE decreased the OR for multiple DIULs and was associated with a more proximal location of ESCC. In conclusion, the detection of DIULs in an alcohol-dependent population decreased between 2003 and 2018. In addition to reported determinants of ESCC, CAG and HH/CLE were associated with the risk of DIULs. Enigmatically, however, the decline in the detection of DIULs was not adequately explained by these factors and warrants further research.

Genetic Biomarkers of Barrett's Esophagus Susceptibility and Progression to Dysplasia and Cancer: A Systematic Review and Meta-Analysis.

Barrett's esophagus (BE) is a common and important precursor lesion of esophageal adenocarcinoma (EAC). A third of patients with BE are asymptomatic, and our ability to predict the risk of progression of metaplasia to dysplasia and EAC (and therefore guide management) is limited. There is an urgent need for clinically useful biomarkers of susceptibility to both BE and risk of subsequent progression. This study aims to systematically identify, review, and meta-analyze genetic biomarkers reported to predict both. A systematic review of the PubMed and EMBASE databases was performed in May 2014. Study and evidence quality were appraised using the revised American Society of Clinical Oncology guidelines, and modified Recommendations for Tumor Marker Scores. Meta-analysis was performed for all markers assessed by more than one study. A total of 251 full-text articles were reviewed; 52 were included. A total of 33 germline markers of susceptibility were identified (level of evidence II-III); 17 were included. Five somatic markers of progression were identified; meta-analysis demonstrated significant associations for chromosomal instability (level of evidence II). One somatic marker of progression/relapse following photodynamic therapy was identified. However, a number of failings of methodology and reporting were identified. This is the first systematic review and meta-analysis to evaluate genetic biomarkers of BE susceptibility and risk of progression. While a number of limitations of study quality temper the utility of those markers identified, some-in particular, those identified by genome-wide association studies, and chromosomal instability for progression-appear plausible, although robust validation is required.

Gastro-Esophageal Junction Precancerosis: Histological Diagnostic Approach and Pathogenetic Insights.

Barrett's esophagus (BE) was initially defined in the 1950s as the visualization of gastric-like mucosa in the esophagus. Over time, the definition has evolved to include the identification of goblet cells, which confirm the presence of intestinal metaplasia within the esophagus. Chronic gastro-esophageal reflux disease (GERD) is a significant risk factor for adenocarcinoma of the esophagus, as intestinal metaplasia can develop due to GERD. The development of adenocarcinomas related to BE progresses in sequence from inflammation to metaplasia, dysplasia, and ultimately carcinoma. In the presence of GERD, the squamous epithelium changes to columnar epithelium, which initially lacks goblet cells, but later develops goblet cell metaplasia and eventually dysplasia. The accumulation of multiple genetic and epigenetic alterations leads to the development and progression of dysplasia. The diagnosis of BE requires the identification of intestinal metaplasia on histologic examination, which has thus become an essential tool both in the diagnosis and in the assessment of dysplasia's presence and degree. The histologic diagnosis of BE dysplasia can be challenging due to sampling error, pathologists' experience, interobserver variation, and difficulty in histologic interpretation: all these problems complicate patient management. The development and progression of Barrett's esophagus (BE) depend on various molecular events that involve changes in cell-cycle regulatory genes, apoptosis, cell signaling, and adhesion pathways. In advanced stages, there are widespread genomic abnormalities with losses and gains in chromosome function, and DNA instability. This review aims to provide an updated and comprehensible diagnostic approach to BE based on the most recent guidelines available in the literature, and an overview of the pathogenetic and molecular mechanisms of its development.

Epidemiology of Barrett's Esophagus and Esophageal Carcinoma.

To care and treat patients with esophageal cancer, one must first understand the epidemiology of Barrett's esophagus (BE). BE is defined as the intestinal metaplasia occurring within the esophagus from normal squamous epithelium to abnormal specialized columnar epithelium. BE, while first described by Allison in 1948, was attributed to Norman Barrett in 1950, who reported a case of chronic peptic ulcer in the lower esophagus that was covered by columnar epithelium.

CD80 expression promotes immune surveillance in Barrett's metaplasia.

Esophageal adenocarcinoma (EAC) is the final step of a pathway starting with esophageal reflux disease, Barrett's metaplasia and Barrett's dysplasia. Positive costimulatory ligands such as CD80 have been suggested to contribute to anti-tumor T-cell efficacy. Here we report for the first time the role of CD80 in the inflammatory esophageal carcinogenesis and characterize the immune environment of EAC. Mucosa samples from cancer were obtained during esophagectomy from patients affected by EAC. Fresh biopsies were obtained from patients who underwent endoscopy for screening or follow-up. A rodent model of reflux induced esophageal carcinogenesis was created with an esophago-gastro-jejunostomy. CD80 expression was increased in epithelial cells during metaplasia in the inflammatory esophageal carcinogenesis cascade. Cd80 null mice as well as WT mice that received antiCD80 antibodies showed a higher rate of dysplasia and KI-67+ cells. These results suggest that CD80 mediates an active immune surveillance process in early inflammation-driven esophageal carcinogenesis.

Increased detection of Barrett's esophagus and esophageal dysplasia with adjunctive use of wide-area transepithelial sample with three-dimensional computer-assisted analysis (WATS).

BACKGROUND: Barrett's esophagus (BE) and esophageal dysplasia (ED) are frequently missed during screening and surveillance esophagoscopy because of sampling error associated with four-quadrant random forceps biopsy (FB). AIM: The aim of this article is to determine if wide-area transepithelial sampling with three-dimensional computer-assisted analysis (WATS) used adjunctively with FB can increase the detection of BE and ED. METHODS: In this multicenter prospective trial, patients screened for suspected BE and those with known BE undergoing surveillance were enrolled. Patients at 25 community-based practices underwent WATS adjunctively to targeted FB and random four-quadrant FB. RESULTS: Of 4203 patients, 594 were diagnosed with BE by FB alone, and 493 additional cases were detected by adding WATS, increasing the overall detection of BE by 83% (493/594, 95% CI 74%-93%). Low-grade dysplasia (LGD) was diagnosed in 26 patients by FB alone, and 23 additional cases were detected by adding WATS, increasing the detection of LGD by 88.5% (23/26, 95% CI 48%-160%). CONCLUSIONS: Adjunctive use of WATS to FB significantly improves the detection of both BE and ED. Sampling error, an inherent limitation associated with screening and surveillance, can be improved with WATS allowing better informed decisions to be made about the management and subsequent treatment of these patients.

Precision care for Barrett's esophagus.

Modern recognition and management of Barrett's esophagus, a precursor to esophageal adenocarcinoma depends on diagnostic accuracy, risk assessment, technical expertise and consideration of many options to best tailor therapy for every patient. Concomitant management of acid reflux is essential, frequently with proton pump inhibitors. Ablation and resection favorably affect the evolution towards cancer. Using precision medicine tools, such as imaging, molecular diagnostics and analytics may lead to cost- and comparatively-effective therapies ultimately aiming at cancer prevention. Knowledge of the risk factors for Barrett's esophagus and progression to dysplasia and cancer can help tailor a precision medicine approach with more aggressive screening and surveillance targeted at patients that are most likely to benefit.

Emerging endoscopic techniques for the identification of esophageal disease.

Esophageal diseases, both benign and malignant, impose an increasing burden to global health. In the West, gastroesophageal reflux disease (GERD) and Barrett's esophagus are increasing in prevalence and impact. In the East, squamous esophageal cancer remains a large burden, but increasingly, precancerous lesions related to GERD are recognized. We review the various advanced endoscopic techniques that have been developed to improve the accuracy of endoscopic identification of esophageal disease. These techniques are designed to increase the sensitivity of detecting disease and high-risk lesions, enable targeted biopsies, decrease total number of biopsies and costs for surveillance, but also guide therapy in real-time. After proper clinical validation, the widespread use of these technologies will lead to improved outcomes, mostly in cancer prevention.

Ablación con radiofrecuencia del esófago de Barret con displasia o carcinoma in situ: Experiencia preliminar / Preliminary Experience with Radiofrequency Ablation of Barrett’s Esophagus with in situ Dysplasia or Carcinoma

Introducción: el esófago de Barrett (EB) es el resultado de la injuria crónica del ácido sobre el epitelio esofágico por el RGE. Se define cuando el epitelio metaplásico columnar reemplaza al epitelio escamoso estratificado que normalmente recubre el esófago. El EB representa un factor de riesgo para el adenocarcinoma de esófago. El objetivo de la ablación por radiofrecuencia (RFA) es destruir el epitelio metaplásico con la corriente eléctrica de radiofrecuencia para estimular la reaparición del epitelio plano estratificado del esófago distal. Objetivo: evaluar la eficiencia y seguridad de la técnica de RFA, recientemente introducida en la ciudad de Medellín, Colombia, para el manejo del EB con displasia o carcinoma in situ. Materiales y métodos: diez pacientes fueron tratados con RFA. Pacientes con EB con displasia o carcinoma in situ como hallazgo histológico fueron elegidos para el tratamiento. La técnica de RFA se aplicó usando el equipo BARRX: el sistema circular HALO360 o el HALO90. Los efectos macro o microscópicos de la terapia con RFA, la tolerancia del paciente al tratamiento así como las complicaciones fueron evaluadas. Resultados: un grupo de 10 pacientes recibió la terapia con RFA, todos terminaron la terapia y el seguimiento. En siete pacientes había displasia de bajo grado, en dos de alto grado y un paciente con carcinoma in situ. Dos pacientes tenían resección endoscópica con bandas de nódulos de la mucosa previa a la terapia con RFA. Se realizaron un total de 13 procedimientos: 10 con HALO360, 2 HALO90 y un paciente tratado con argón plasma para un EB residual. En todos los pacientes se logró la erradicación del epitelio esofágico metaplásico y displásico como se confirmó en la evaluación endoscópica e histológica. No se encontraron complicaciones significativas relacionadas con la terapia de RFA, pero en dos pacientes se encontró estenosis del esófago y uno requirió dilataciones endoscópicas tres semanas después de la terapia. Conclusiones: con base en estos resultados preliminares consideramos que este es un método promisorio, sin mayores complicaciones y bien tolerado por el paciente. En la mayoría de pacientes se erradicó exitosamente el epitelio metaplásico y displásico del esófago distal.

Introduction: Barrett’s esophagus (BE) is the result of chronic damage to the esophageal epithelium caused by the acid of gastrointestinal reflux diseases (GERD). It is defined as replacement of the by stratified squamous epithelium that normally lines the esophagus with metaplastic columnar epithelium. BE represents a risk factor for esophageal adenocarcinoma. The aim of radiofrequency ablation (RFA) is to destroy the metaplastic epithelium with the electric current of a radiofrequency to stimulate the reappearance of stratified squamous epithelium in the distal esophagus. Objective: The objective of this study was to evaluate the efficiency and safety of RFA which has recently been introduced in the city of Medellin, Colombia for management of BE with in situ dysplasia or carcinoma. Materials and Methods: Ten patients were treated with RFA. BE patients with in situ dysplasia or carcinoma and histological diagnoses were chosen for treatment. RFA procedures were done with BARRX equipment, the circular HALO360 system or the HALO90 system. Macroscopic and microscopic effects of RFA, patient tolerance to treatment and complications were evaluated. Results: A group of 10 patients received treatment with RFA. All ten finished treatment and follow-up. Seven patients had low-grade dysplasia, two had high-grade dysplasia, and one patient had in situ carcinoma. Two patients had undergone endoscopic resections of nodules and treatments of mucosa with bands prior to therapy with RFA. A total of 13 procedures were performed: 10 RFAs with the HALO360, 2 RFAs with the HALO90 and one argon plasma treatment for residual BE in one patient. Eradication of metaplastic and dysplastic esophageal epithelium was achieved in all patients and confirmed by endoscopic and histologic evaluation. No significant complications related to RFA were found, but in two patients esophageal stenoses were found. One required endoscopic dilatation three weeks after therapy. Conclusions: Based on these preliminary results we believe that this is a promising method that is well-tolerated by patients and which has no major complications. Metaplastic and dysplastic epithelium of the distal esophagus were successfully eradicated in most patients.