Barrett Esophageal Adenocarcinoma Research Articles

507. LONG BARRETT´S ESOPHAGUS IN MONOZYGOTIC TWINS WITH ADENOCARCINOMA DEVELOPMENT

Abstract Background Familial aggregation of Barrett's esophagus (BE) and esophageal adenocarcinoma (EA) suggests a genetic pattern in fewer than 10% of patients with the former diseases. In 1983, BE was described in identical twins, underlining the hereditary influence on the development of mucosal dysplasia in some patients with this epithelial alteration. At present, some studies have attempted to identify chromosomal alterations among patients with familial aggregation of BE or EA, but there is not a clear pattern. Methods Description of the case report of a male patient who underwent esophagectomy due to EA on a long BE, who had a monozygotic twin without gastroesophageal reflux symptoms and no upper GI endoscopies before. Results A 53-year-old man was diagnosed with EA and a long BE (8 cm length) in 2017. He underwent CROSS neoadjuvant treatment and minimally invasive Ivor-Lewis esophagectomy. The pathological report indicated a GI T3N1M0 adenocarcinoma. Unfortunately, the patient developed lung metastases and passed away in 2019. Before that, the patient recalled that he had an identical twin brother with no gastroesophageal reflux symptoms, but we decided to scope him in 2017. The gastroscopy report revealed a 2 cm hiatal hernia with a long BE (C4M6 Prague Classification) but with no dysplasia. Nowadays, the twin patient is under close follow-up with proton pump inhibitors (PPI) and has not developed dysplasia. Conclusion Monozygotic twins provide a perfect model to study the possible influence of genetic predisposition to develop BE and EA. The development of EA in a patient guided us to diagnose and treat a long BE in his asymptomatic identical twin. More studies should be done to find the possible genetic alterations linked to familial aggregation of BE and EA.

787. THE CHALLENGE OF GASTRO-ESOPHAGEAL ONCOLOGICAL SURGERY AFTER BARIATRIC PROCEDURES: EXPERIENCE OF A REFERRAL HIGH-VOLUME UPPER GI SURGICAL CENTER

Abstract Background The effectiveness of bariatric surgery for weight loss in morbidly obese patients has been well established and it's becoming more common as many surgeons are trained to perform them safely, even in older patients. Obesity is associated with reflux and hormonal imbalances that increase the risk of Barrett's esophagus, esophageal adenocarcinoma and gastric cancer. Bariatric procedures alter gastric anatomy, vascularization and lymphatic drainage and render subsequent upper gastrointestinal surgery for malignancies a technical challenge, that will present more and more in the future. We present laparoscopic sleeve gastrectomy, gastric bypass and gastric banding conversion to oncological respective surgeries. Methods We retrospectively reviewed the medical records of our referral high-volume center for upper gastrointestinal surgery and identified patients who underwent upper gastrointestinal oncologic surgery from January 1998 to May 2024. We selected all patients who had previously undergone bariatric surgery (laparoscopic sleeve gastrectomy, laparoscopic gastric bypass, gastric banding, or other less common procedures). Three patients met our criteria, and we recorded: demographic characteristics, surgical technique, oncologic surgical outcome, postoperative complications, long-term complications, and oncologic follow-up. Results A hybrid IvorLewis esophagectomy was performed years after a sleeve gastrectomy for distal esophageal adenocarcinoma. The sleeve was used for gastric pull-up, adequately vascularized by the right gastroepiploic artery as demonstrated by intraoperative indocyanine green. A patient developed adenocarcinoma of the cardia after Roux-en-Y gastric bypass, infiltrating the gastric pouch, the gastric remnant and liver S2. After neoadjuvant chemotherapy, an open Ivor-Lewis esophagectomy was performed using the gastric remnant for a pull-up. In a third patient, a locally advanced adenocarcinoma of the stomach developed after gastric banding. After neoadjuvant chemotherapy, an open total gastrectomy with Roux-en-Y esophagojejunostomy was performed. Conclusion We report three cases of successful esophago-gastric oncological surgery in patients with altered anatomy and vascularization due to previous bariatric surgery, without major postoperative complications or mortality. Oncologic benchmarks for both esophageal and gastric surgery were met as a high lymph node yield and oncologic margins were maintained. Our heterogeneous series suggests that sleeve gastrectomy, gastric bypass, and gastric banding surgery can be successfully converted to resective surgeries after a metachronous neoplasia diagnosis in high-volume upper gastrointestinal centers. These and similar modified reconstructive techniques are likely to be used in the future as metabolic surgery and esophago-gastric cancer are increasing.

Optimizing Gastroesophageal Reflux Disease treatment: A call to shift from omeprazole.

Gastroesophageal reflux disease (GERD) is a disorder of the upper respiratory tract, which develops due to the regurgitation of acid from the stomach into the oesophagus. If left untreated, GERD may cause serious complications such as Barrett's oesophagus, oesophageal strictures, and oesophageal adenocarcinoma. According to a study published by Nirwan JS et al in 2020, individuals suffering from Gastroesophageal reflux disease globally is 1.03 billion.[1] Proton pump inhibitors (PPIs) are frequently used drugs for the treatment of GERD. Omeprazole belongs to PPIs class of drugs and it has been a drug of choice for GERD because it is affordable, easily available, and it can be taken along with other medicines. However, Proton pump inhibitors are not completely risk-free, chronic use of Proton Pump inhibitors has been associated with decreased calcium and magnesium absorption increasing the risk of osteoporosis and electrolyte disturbances respectively. It also increases the risk of community-acquired pneumonia [2] However, Esomeprazole the s-isomer of omeprazole yields much better results than omeprazole. It is more effective and safe in the treatment of GERD, not only does it decrease the symptoms of the disease rapidly ie. heartburn [4] but also it reduces the relapse of the symptoms twice that of omeprazole. Maintenance of intragastric pH > 4 is an effective measure for the management of gastroesophageal reflux disease, esomeprazole has demonstrated improved acid inhibition over omeprazole with a high mean percentage of 24-hour intragastric pH > 4. The healing rate for reflux esophagitis and relapse was also higher for esomeprazole than that of omeprazole.[3] According to a study, the number of individuals with GERD in the South Asia region is around 8000 per 100000 [4]. Knowing the extent of Gastroesophageal patients present in Pakistan and how rapidly this number can escalate due to poor lifestyle modifications. Omeprazole which is the most frequent drug prescribed for the treatment of GERD [5] should be discouraged and Esomeprazole being more beneficial in terms of healing time and relapse of symptoms should be promoted to prevent chronic use adverse effects of Proton pump inhibitors. Overall, such a measure will improve the quality of life of a person suffering from gastroesophageal reflux disease which otherwise may lead to more severe implications.

Analytical Validation of a DNA Methylation Biomarker Test for the Diagnosis of Barrett's Esophagus and Esophageal Adenocarcinoma from Samples Collected Using EsoCheck®, a Non-Endoscopic Esophageal Cell Collection Device.

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.

Endoscopic Diagnosis and Treatment of Early Mucosal Neoplasms in the Oesophagus

Endoscopy is the gold standard for diagnosis of oesophageal cancer and its precursor lesions. Besides this, endoscopy treatment of these precursor lesions and early oesophageal cancer has been well evaluated and established. This includes dysplastic lesions associated with Barrett's oesophagus and early adenocarcinoma, as well as early squamous cell cancer of the oesophagus. The role of endoscopy for diagnosis and treatment of these lesions is summarised.

Nonendoscopic Screening for Barrett's Esophagus and Esophageal Adenocarcinoma in At-Risk Veterans.

Although rates of esophageal adenocarcinoma (EAC) in the United States continue to rise, many patients at risk of disease are not screened. EsoCheck (EC), a nonendoscopic esophageal balloon sampling device coupled with EsoGuard (EG), a DNA-based screening assay, is an US Food and Drug Administration-approved minimally invasive alternative to the traditional screening method of upper endoscopy. The objective of this study was to prospectively determine the diagnostic accuracy, tolerance, and acceptability of the EC/EG test in a screening population. We recruited veterans who met the American College of Gastroenterology Guideline criteria for endoscopic Barrett's esophagus (BE) and EAC screening at the Louis Stokes Cleveland Veterans Affairs Medical Center. All study participants completed unsedated EC-guided distal esophageal sampling followed by a sedated esophagogastroduodenoscopy (EGD). Diagnostic yield of the EG assay and EGD was recorded and used in calculation of sensitivity and specificity of EC/EG in prospective screening. The abbreviated Spielberger State-Trait Anxiety Inventory questionnaire was administered before and after completion of EC. Overall tolerance of EC sampling was evaluated on a 10-point Likert scale. Esophageal cancer screening was accepted by 130 of 782 eligible veterans (16.6%), and we analyzed results of those who completed both screening tests (N = 124). Prevalence of BE/EAC among studied veterans was 12.9% (16/124), based on EGD. Sensitivity and specificity of EC/EG for EGD-detected BE/EAC were 92.9% (95% confidence interval [CI] 66.1-99.8) and 72.2% (95% CI 62.1-80.8), respectively. Positive and negative predictive values were 32.5% (95% CI 18.6-49.1) and 98.6% (95% CI 92.4-100), respectively. Baseline Spielberger State-Trait Anxiety Inventory-6 scores were reflective of notable levels of anxiety among veterans in the periprocedural setting. The mean postprocedure acceptability score for the EC test was 7.23 (SD 2.45). Our data suggest excellent sensitivity and negative predictive value of EC/EG in a screening population of veterans, making this modality a powerful screening tool for BE and EAC.

Endoscopic Advances in the Diagnosis and Management of Gastroesophageal Reflux Disease.

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.

Prevalence of Gastroesophageal Reflux Disease in Congenital Diaphragmatic Hernia Survivors From Infancy to Adulthood

BackgroundGastroesophageal reflux disease (GERD) is a common comorbidity associated with congenital diaphragmatic hernia (CDH), with reported cases of Barrett's esophagus (BE) and esophageal adenocarcinoma before the age of 25. The prevalence and natural course of GERD in CDH survivors remain uncertain due to variations in diagnostic methods. We aimed to analyse the GERD prevalence from infancy through young adulthood. MethodsWe retrospectively analyzed pH-impedance measurements and endoscopic findings in 96 CDH survivors evaluated as routine care using well established clinical protocols.GERD was defined as an abnormal acid exposure time for pH-MII measurements and as presence of reflux esophagitis or BE at upper endoscopy. Clinical data including symptoms at time of follow-up and use of antireflux medication were collected. ResultsGERD prevalence remained consistently low (≤10%) across all age groups, yet many patients experienced GER symptoms. Histological abnormalities were observed in 80% of adolescents and young adults, including microscopic esophagitis in 50%. BE was diagnosed in 7% before the age of 18, all had GER symptoms. CDH severity, anatomy at the time of CDH correction, alcohol usage, and smoking did not emerge as significant risk factors for GERD. ConclusionsGiven the low GERD prevalence in CDH survivors, a symptom-driven approach to diagnosis and follow-up is warranted. We advise long-term follow-up for all adult patients due to the early onset of BE and the limited evidence available. The longitudinal course and impact of GERD on other long-term CDH-related comorbidities should be explored in larger cohorts. Level of EvidenceNot applicable

Multicenter, Prospective Trial of Nonendoscopic Biomarker-Driven Detection of Barrett's Esophagus and Esophageal Adenocarcinoma.

Preliminary data suggest that an encapsulated balloon (EsoCheck), coupled with a 2 methylated DNA biomarker panel (EsoGuard), detects Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) with high accuracy. The initial assay requires sample freezing upon collection. The purpose of this study was to assess a next-generation EsoCheck sampling device and EsoGuard assay in a much-enlarged multicenter study clinically enhanced by using a Clinical Laboratory Improvement Amendments of 1988-compliant assay and samples maintained at room temperature. Cases with nondysplastic BE (NDBE), dysplastic BE (indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia), EAC, junctional adenocarcinoma, plus endoscopy controls without esophageal intestinal metaplasia, were prospectively enrolled. Medical assistants at 6 institutions delivered the encapsulated balloon per orally with inflation in the stomach. The inflated balloon sampled the distal 5 cm of the esophagus and then was deflated and retracted into the capsule, preventing sample contamination. EsoGuard bisulfite sequencing assayed levels of methylated vimentin and methylated cyclin A1. A total of 243 evaluable patients-88 cases (median age 68 years, 78% men, 92% White) and 155 controls (median age 57 years, 41% men, 88% White)-underwent adequate EsoCheck sampling. The mean procedural time was approximately 3 minutes. Cases included 31 with NDBE, 16 with indefinite for dysplasia/low-grade dysplasia, 23 with high-grade dysplasia, and 18 with EAC/junctional adenocarcinoma. Thirty-seven NDBE and dysplastic BE cases (53%) were short-segment BE (<3 cm). Overall sensitivity was 85% (95% confidence interval 0.78-0.93) and specificity was 85% (95% confidence interval 0.79-0.90). Sensitivity for NDBE was 84%. EsoCheck/EsoGuard detected 100% of cancers (n = 18). EsoCheck/EsoGuard demonstrated high sensitivity and specificity in detecting BE and BE-related neoplasia.

Long- vs short-segment Barrett's esophagus-derived adenocarcinoma: clinical features and outcomes of endoscopic submucosal dissection.

The incidence of Barrett's esophageal adenocarcinoma (BEA) is increasing, and endoscopic submucosal dissection (ESD) has been frequently performed for its treatment. However, the differences between the characteristics and ESD outcomes between short- and long-segment BEA (SSBEA and LSBEA, respectively) are unclear. We compared the clinicopathological characteristics and short- and long-term outcomes of ESD between both groups. We retrospectively reviewed 155 superficial BEAs (106 SSBEAs and 49 LSBEAs) treated with ESD in 139 patients and examined their clinicopathological features and ESD outcomes. SSBEA and LSBEA were classified based on whether the maximum length of the background mucosa of BEA was < 3cm or ≥ 3cm, respectively. Compared with SSBEA, LSBEA showed significantly higher proportions of cases with the macroscopically flat type (36.7% vs. 5.7%, p < 0.001), left wall location (38.8% vs. 11.3%, p < 0.001), over half of the tumor circumference (20.4% vs. 1.9%, p < 0.001), and synchronous lesions (17.6% vs. 0%, p < 0.001). Compared with SSBEA, regarding ESD outcomes, LSBEA showed significantly longer resection duration (91.0min vs. 60.5min, p < 0.001); a lower proportion of submucosal invasion (14.3% vs. 29.2%, p = 0.047), horizontal margin negativity (79.6% vs. 94.3%, p = 0.0089), and R0 resection (69.4% vs. 86.8%, p = 0.024); and a higher proportion of post-procedural stenosis cases (10.9% vs. 1.9%, p = 0.027). The 5-year cumulative incidence of metachronous cancer in patients without additional treatment was significantly higher for LSBEA than for SSBEA (25.0% vs. 0%, p < 0.001). The clinicopathological features of LSBEA and SSBEA and their treatment outcomes differed in many aspects. As LSBEAs are difficult to diagnose and treat and show a high risk of metachronous cancer development, careful ESD and follow-up or eradication of the remaining BE may be required.

Decoding common genetic alterations between Barrett's esophagus and esophageal adenocarcinoma: A bioinformatics analysis

BackgroundEsophageal adenocarcinoma (EAC) is a common cancer with a poor prognosis in advanced stages. Therefore, early EAC diagnosis and treatment have gained attention in recent decades. It has been found that various pathological changes, particularly Barrett's Esophagus (BE), can occur in the esophageal tissue before the development of EAC. In this study, we aimed to identify the molecular contributor in BE to EAC progression by detecting the essential regulatory genes that are differentially expressed in both BE and EAC. Materials and methodsWe conducted a comprehensive bioinformatics analysis to detect BE and EAC-associated genes. The common differentially expressed genes (DEGs) and common single nucleotide polymorphisms (SNPs) were detected using the GEO and DisGeNET databases, respectively. Then, hub genes and the top modules within the protein-protein interaction network were identified. Moreover, the co-expression network of the top module by the HIPPIE database was constructed. Additionally, the gene regulatory network was constructed based on miRNAs and circRNAs. Lastly, we inspected the DGIdb database for possible interacted drugs. ResultsOur microarray dataset analysis identified 92 common DEGs between BE and EAC with significant enrichment in skin and epidermis development genes. The study also identified 22 common SNPs between BE and EAC. The top module of PPI network analysis included SCEL, KRT6A, SPRR1A, SPRR1B, SPRR3, PPL, SPRR2B, EVPL, and CSTA. We constructed a ceRNA network involving three specific mRNAs, 23 miRNAs, and 101 selected circRNAs. According to the results from the DGIdb database, TD101 was found to interact with the KRT6A gene. ConclusionThe present study provides novel potential candidate genes that may be involved in the molecular association between Esophageal adenocarcinoma and Barrett's Esophagus, resulting in developing the diagnostic tools and therapeutic targets to prevent progression of BE to EAC.

The role of the fibroblast in Barrett's esophagus and esophageal adenocarcinoma.

Barrett's esophagus (BE) is the number one risk factor for developing esophageal adenocarcinoma (EAC), a deadly cancer with limited treatment options that has been increasing in incidence in the US. In this report, we discuss current studies on the role of mesenchyme and cancer-associated fibroblasts (CAFs) in BE and EAC, and we highlight translational prospects of targeting these cells. New insights through studies using single-cell RNA sequencing (sc-RNA seq) have revealed an important emerging role of the mesenchyme in developmental signaling and cancer initiation. BE and EAC share similar stromal gene expression, as functional classifications of nonepithelial cells in BE show a remarkable similarity to EAC CAFs. Several recent sc-RNA seq studies and novel organoid fibroblast co-culture systems have characterized the subgroups of fibroblasts in BE and EAC, and have shown that these cells can directly influence the epithelium to induce BE development and cancer progression. Targeting the CAFs in EAC with may be a promising novel therapeutic strategy. The fibroblasts in the surrounding mesenchyme may have a direct role in influencing altered epithelial plasticity during BE development and progression to EAC.

Risk stratification for synchronous/metachronous recurrence after endoscopic submucosal dissection for Barrett's esophageal adenocarcinoma using the length of Barrett's esophagus.

In Japan, the standard management of Barrett's esophageal adenocarcinoma after endoscopic submucosal dissection involves follow-up; however, multifocal synchronous/metachronous lesions are sometimes observed after endoscopic submucosal dissection. Risk stratification of multifocal cancer facilitates appropriate treatment, including eradication of Barrett's esophagus in high-risk cases; however, no effective risk stratification methods have been established. Thus, we identified the risk factors for multifocal cancer and explored risk-stratified treatment strategies for residual Barrett's esophagus. We retrospectively reviewed the data of 97 consecutive patients with superficial Barrett's esophageal adenocarcinomas who underwent curative resection with endoscopic submucosal dissection. Multifocal cancer was defined by the presence of synchronous/metachronous lesions during follow-up. We used Cox regression analysis to identify the risk factors for multifocal cancer and subsequently analyzed differences in cumulative incidences. The cumulative incidences of multifocal cancer at 1, 3, and 5years were 4.4%, 8.6%, and 10.7%, respectively. Significant risk factors for multifocal cancer were increased circumferential and maximal lengths of Barrett's esophagus. The cumulative incidences of multifocal cancer at 3years were lower for patients with circumferential length < 4cm and maximal length < 5cm (2.9% and 1.2%, respectively) than for patients with circumferential length ≥ 4cm and maximal length ≥ 5cm (51.5% and 49.1%, respectively). Risk stratification of multifocal cancer using length of Barrett's esophagus was effective. Further multicenter prospective studies are needed to substantiate our findings.

Development of an Artificial Intelligence Diagnostic System Using Linked Color Imaging for Barrett's Esophagus.

Background: Barrett's esophagus and esophageal adenocarcinoma cases are increasing as gastroesophageal reflux disease increases. Using artificial intelligence (AI) and linked color imaging (LCI), our aim was to establish a method of diagnosis for short-segment Barrett's esophagus (SSBE). Methods: We retrospectively selected 624 consecutive patients in total at our hospital, treated between May 2017 and March 2020, who experienced an esophagogastroduodenoscopy with white light imaging (WLI) and LCI. Images were randomly chosen as data for learning from WLI: 542 (SSBE+/- 348/194) of 696 (SSBE+/- 444/252); and LCI: 643 (SSBE+/- 446/197) of 805 (SSBE+/- 543/262). Using a Vision Transformer (Vit-B/16-384) to diagnose SSBE, we established two AI systems for WLI and LCI. Finally, 126 WLI (SSBE+/- 77/49) and 137 LCI (SSBE+/- 81/56) images were used for verification purposes. The accuracy of six endoscopists in making diagnoses was compared to that of AI. Results: Study participants were 68.2 ± 12.3 years, M/F 330/294, SSBE+/- 409/215. The accuracy/sensitivity/specificity (%) of AI were 84.1/89.6/75.5 for WLI and 90.5/90.1/91.1/for LCI, and those of experts and trainees were 88.6/88.7/88.4, 85.7/87.0/83.7 for WLI and 93.4/92.6/94.6, 84.7/88.1/79.8 for LCI, respectively. Conclusions: Using AI to diagnose SSBE was similar in accuracy to using a specialist. Our finding may aid the diagnosis of SSBE in the clinic.

Obesity and Upper Gastrointestinal Diseases.

Obesity increases gastroesophageal reflux disease through several factors. As a result, Barrett's esophagus, esophageal adenocarcinoma, and gastroesophageal junctional gastric cancer are increasing. Existing studies usually defined obesity by body mass index and analyzed the correlation. Recently, more studies have shown that central obesity is a more important variable in upper gastrointestinal diseases related to gastroesophageal reflux. Studies have reported that weight loss is effective in reducing gastroesophageal reflux symptoms. Obesity also affects functional gastrointestinal diseases. A significant correlation was shown in upper abdominal pain, reflux, vomiting, and diarrhea rather than lower abdominal diseases.

Algorithm Training and Testing for a Nonendoscopic Barrett’s Esophagus Detection Test in Prospective Multicenter Cohorts

Endoscopic Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) detection is invasive and expensive. Nonendoscopic BE/EAC detection tools are guideline-endorsed alternatives. We previously described a 5-methylated DNA marker (MDM) panel assayed on encapsulated sponge cell collection device (CCD) specimens. We aimed to train a new algorithm using a 3-MDM panel and test its performance in an independent cohort. Algorithm training and test samples were from 2 prospective multicenter cohorts. All BE cases had esophageal intestinal metaplasia (with or without dysplasia/EAC); control subjects had no endoscopic evidence of BE. The CCD procedure was followed by endoscopy. From CCD cell lysates, DNA was extracted, bisulfite treated, and MDMs were blindly assayed. The algorithm was set and locked using cross-validated logistic regression (training set) and its performance was assessed in an independent test set. Training (N= 352) and test (N= 125) set clinical characteristics were comparable. The final panel included 3 MDMs (NDRG4, VAV3, ZNF682). Overall sensitivity was 82% (95% CI, 68%-94%) at 90% (79%-98%) specificity and 88% (78%-94%) sensitivity at 84% (70%-93%) specificity in training and test sets, respectively. Sensitivity was 90% and 68% for all long- and short-segment BE, respectively. Sensitivity for BE with high-grade dysplasia and EAC was 100% in training and test sets. Overall sensitivity for nondysplastic BE was 82%. Areas under the receiver operating characteristic curves for BE detection were 0.92 and 0.94 in the training and test sets, respectively. A locked 3-MDM panel algorithm for BE/EAC detection using a nonendoscopic CCD demonstrated excellent sensitivity for high-risk BE cases in independent validation samples. (Clinical trials.gov: NCT02560623, NCT03060642.).

Endoscopic Diagnosis and Treatment of Early Mucosal Neoplasms in the Oesophagus

Endoscopy is the gold standard for diagnosis of oesophageal cancer and its precursor lesions. Besides this, endoscopy treatment of these precursor lesions and early oesophageal cancer has been well evaluated and established. This includes dysplastic lesions associated with Barrett's oesophagus and early adenocarcinoma, as well as early squamous cell cancer of the oesophagus. The role of endoscopy for diagnosis and treatment of these lesions is summarised.

Prebiotic proanthocyanidins inhibit bile reflux-induced esophageal adenocarcinoma through reshaping the gut microbiome and esophageal metabolome.

The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammation-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome-esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague-Dawley rats, with or without reflux induction, received water or C-PAC ad libitum (700 μg/rat/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR/NF-κB/TP53 signaling cascades. At the species level, C-PAC mitigated reflux-induced pathogenic bacteria (Streptococcus parasanguinis, Escherichia coli, and Proteus mirabilis). C-PAC specifically reversed reflux-induced bacterial, inflammatory, and immune-implicated proteins and genes, including Ccl4, Cd14, Crp, Cxcl1, Il6, Il1b, Lbp, Lcn2, Myd88, Nfkb1, Tlr2, and Tlr4, aligning with changes in human EAC progression, as confirmed through public databases. C-PAC is a safe, promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation, and cellular damage.

On-chip Raman spectroscopy of live single cells for the staging of oesophageal adenocarcinoma progression.

The absence of early diagnosis contributes to oesophageal cancer being the sixth most common cause of global cancer-associated deaths, with a 5-year survival rate of < 20%. Barrett's oesophagus is the main pre-cancerous condition to adenocarcinoma development, characterised by the morphological transition of oesophageal squamous epithelium to metaplastic columnar epithelium. Early tracking and treatment of oesophageal adenocarcinoma could dramatically improve with diagnosis and monitoring of patients with Barrett's Oesophagus. Current diagnostic methods involve invasive techniques such as endoscopies and, with only a few identified biomarkers of disease progression, the detection of oesophageal adenocarcinoma is costly and challenging. In this work, single-cell Raman spectroscopy was combined with microfluidic techniques to characterise the development of oesophageal adenocarcinoma through the progression of healthy epithelial, Barrett's oesophagus and oesophageal adenocarcinoma cell lines. Principal component analysis and linear discriminant analysis were used to classify the different stages of cancer progression. with the ability to differentiate between healthy and cancerous cells with an accuracy of 97%. Whilst the approach could also separate the dysplastic stages from healthy or cancer with high accuracy-the intra-class separation was approximately 68%. Overall, these results highlight the potential for rapid and reliable diagnostic/prognostic screening of Barrett's Oesophagus patients.

A case of Barrett's esophageal adenocarcinoma that could not be detected early with a small-caliber endoscope

A case of Barrett's esophageal adenocarcinoma that could not be detected early with a small-caliber endoscope