Esophageal Adenocarcinoma Research Articles

Highlights on gastroesophageal tumors: the comeback of FLOT

Summary This article aims to summarize the highlights of the two largest global congresses of 2024 with respect to gastroesophageal tumors. The triplet chemotherapy combination known as FLOT (5-fluorouracil, leucovorin, oxaliplatin, docetaxel), used as perioperative chemotherapy, was demonstrated to improve overall and disease-free survival in resectable gastroesophageal cancer patients some time ago. Despite being standard for this patient population, many questions for different scenarios remain open: Is FLOT also efficacious in patients with esophageal or gastroesophageal junction adenocarcinoma when compared to neoadjuvant chemoradiotherapy? Is FLOT a feasible chemotherapy option for oligometastatic patients, thereby contributing to the overall survival as “neoadjuvant” treatment before palliative resection? Can the efficacy of FLOT be strengthened by applying additional radiation treatment to patients with gastroesophageal adenocarcinoma? Is FLOT really necessary in the adjuvant setting for all patients, or can the adjuvant treatment be guided based on pathological response rates? These questions were answered to some extent in the ESOPEC and RENAISSANCE trials at the American Society of Clinical Oncology (ASCO) meeting and the TOPGEAR and SPACE-FLOT trials at European Society for Medical Oncology (ESMO) meeting. Many other FLOT-related studies for resectable as well as metastatic gastroesophageal cancer patients are yet to come.

CCN1 promotes APRIL/BAFF signaling in esophageal squamous cell carcinoma but attenuates it in esophageal adenocarcinoma

CCN1 is a matricellular protein highly expressed in esophageal squamous cell carcinoma (ESCC) but hardly detectable in esophageal adenocarcinoma (EAC). Expression of CCN1 in EAC cells leads to TRAIL-mediated apoptosis. Unlike TRAIL, which primarily triggers cell death, APRIL and BAFF promote cell growth via NFκB signaling. They become active ligands by Furin cleavage. This study found that CCN1 upregulated APRIL and BAFF expression in both ESCC and EAC cells but attenuated their signaling in the latter. CCN1 kept Furin stable in ESCC allowing APRIL/BAFF to signal through their common receptor BCMA properly. In EAC cells, however, expression of CCN1 lowered Furin activity and thus limited APRIL/BAFF cleavage. As a result, ESCC cells benefited from CCN1 while EAC cell viability was attenuated by it.

Induction Radiochemotherapy for Esophageal Cancer: Long-Term Outcomes from a Single-Center Study

Background/Objectives: The management of esophageal cancer (EC) remains a significant clinical challenge, particularly in optimizing therapeutic strategies for different stages and subgroups. This study assessed the impact of preoperative radiochemotherapy (CRT) on clinical staging and identified subgroups for whom definitive CRT (dCRT) may provide a favorable alternative to surgery. Methods: Sixty-one patients with esophageal adenocarcinoma or squamous cell carcinoma were enrolled. Pre-treatment staging included computed tomography, gastroscopy with biopsy, and comprehensive laboratory evaluations. Patients received preoperative CRT following the CROSS or dCRT protocols based on tumor stage. Surgical approaches included staged esophagectomy or single-stage Ivor Lewis procedures. Four patients declined surgery and were treated with dCRT. Postoperative outcomes were evaluated using pTNM classification. Follow-up included imaging and endoscopic surveillance. Statistical analyses assessed changes in staging and factors influencing treatment outcomes. Results: CRT significantly reduced T stage across the entire cohort (p = 0.0002), with complete pathological response (pT0N0M0) observed in 54.5% of patients following induction CRT (p = 0.0001). Male patients demonstrated a significant reduction in T stage (p = 0.0008), while a similar trend in females was not significant (p = 0.068). Among patients declining surgery, dCRT demonstrated acceptable oncologic control over a mean follow-up of 4 ± 0.79 years. Conclusions: Preoperative CRT effectively downstages EC and achieves high rates of response, especially in male patients. Therefore, dCRT may be a viable alternative in selected patients, emphasizing the need for individualized treatment strategies to optimize outcomes. These findings underscore the importance of refining multimodal approaches in EC care.

Prognostic impact of glucagon-like peptide-1 receptor (GLP1R) expression on cancer survival and its implications for GLP-1R agonist therapy: an integrative analysis across multiple tumor types.

Glucagon-like peptide-1 receptor (GLP-1R) agonists, such as exenatide (Byetta, Bydureon), liraglutide (Victoza, Saxenda), albiglutide (Tanzeum), dulaglutide (Trulicity), lixisenatide (Lyxumia, Adlyxin), semaglutide (Ozempic, Rybelsus, Wegovy), and tirzepatide (Mounjaro, Zepbound), are widely used for the treatment of type 2 diabetes mellitus (T2DM) and obesity. While these agents are well known for their metabolic benefits, there is growing interest in their potential effects on cancer biology. However, the role of GLP-1R agonists in cancer remains complex and not fully understood, particularly across different tumor types. This study aimed to evaluate the prognostic significance of GLP1R expression on overall survival across various cancer types. Using a comprehensive analysis of gene expression data and survival outcomes a large cohorts of different tumor types, we employed Cox proportional hazards survival analyses, coupled with false discovery rate determinations, to explore correlations between GLP1R expression and survival. The integrated database included thousands of cancer specimens with available overall survival time and event data from numerous independent cohorts, providing a robust platform for survival analysis. Our findings reveal that increased GLP1R expression is associated with improved overall survival in cancers such as bladder cancer, breast cancer, esophageal adenocarcinoma, renal clear cell carcinoma, and thyroid carcinoma. Conversely, higher GLP1R expression is linked to poorer survival outcomes in cervical squamous cell carcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. Additionally, GLP1R expression showed no significant impact on overall survival in cancers such as esophageal squamous cell carcinoma, colon cancer, head-neck squamous cell carcinoma, renal papillary cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, ovarian cancer, and pancreatic cancer. In conclusion, GLP1R expression levels serve as an important biomarker with potential prognostic significance across multiple cancers, demonstrating both protective and adverse associations depending on the tumor type. These findings highlight the complex role of GLP-1R agonists in cancer risk and survival, suggesting that the therapeutic use of these agents should be carefully tailored to the individual patient's cancer risk profile.

Effects of CDKN2A loss on evolution of esophageal adenocarcinoma depend on context and time.

Effects of CDKN2A loss on evolution of esophageal adenocarcinoma depend on context and time.

Context-dependent effects of CDKN2A and other 9p21 gene losses during the evolution of esophageal cancer

AbstractCDKN2A is a tumor suppressor located in chromosome 9p21 and frequently lost in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). How CDKN2A and other 9p21 gene co-deletions affect EAC evolution remains understudied. We explored the effects of 9p21 loss in EACs and cancer progressor and non-progressor BEs with matched genomic, transcriptomic and clinical data. Despite its cancer driver role, CDKN2A loss in BE prevents EAC initiation by counterselecting subsequent TP53 alterations. 9p21 gene co-deletions predict poor patient survival in EAC but not BE through context-dependent effects on cell cycle, oxidative phosphorylation and interferon response. Immune quantifications using bulk transcriptome, RNAscope and high-dimensional tissue imaging showed that IFNE loss reduces immune infiltration in BE, but not EAC. Mechanistically, CDKN2A loss suppresses the maintenance of squamous epithelium, contributing to a more aggressive phenotype. Our study demonstrates context-dependent roles of cancer genes during disease evolution, with consequences for cancer detection and patient management.

DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target.

Esophageal adenocarcinoma (EAC) is an aggressive gastrointestinal (GI) malignancy with increasing incidence. Despite the recent progress in targeted therapies and surgical approaches, the survival rates of esophageal adenocarcinoma patients remain poor. The Dickkopf (DKK) proteins are secretory proteins known mainly as antagonists of the Wnt/β-catenin signaling pathway, which is considered an oncogene. However, it has been shown that in several GI cancers, including esophageal cancer, DKK1 may act as an oncogene itself through Wnt-independent signaling pathways. LRP5\6 and Kremen1/2 (Krm1/2) are transmembrane receptors to which the DKK proteins are mainly known to bind. CKAP4 (cytoskeleton-associated protein 4) is a novel receptor of DKK1, and the DKK1-CKAP4 pathway seems to be crucial in the role of DKK1 as an oncogene. The aim of this review is to feature the essential role of DKK1 and its receptors in carcinogenesis with a focus on EAC in an era of urgent need for specific biomarkers along with improved targeted therapies.

Biologically-targeted discovery-replication scan identifies G×G interaction in relation to risk of Barrett's esophagus and esophageal adenocarcinoma.

Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196). ∼75 x 106 SNP×SNP interactions were screened via hierarchical group lasso (glinternet) using BEACON GWAS data. The top ∼2000 interactions retained in each scan were prioritized using P values from single logistic models. Identical scans were repeated among males only (78%), with two independent GWAS datasets used for replication. In overall and male-specific primary replications, 11 of 187 and 20 of 191 interactions satisfied P<0.05, respectively. The strongest evidence for secondary replication was for rs17744726×rs3217992 among males, with consistent directionality across all cohorts (Pmeta=2.19×10-8); rs3217992 "T" was associated with reduced risk only in individuals homozygous for rs17744726 "G". Rs3217992 maps to the CDKN2B 3'UTR and reportedly disrupts microRNA-mediated repression. Rs17744726 maps to an intronic enhancer region in BLK. Through in-silico prioritization and experimental validation, we identified a nearby proxy variant (rs4841556) as a functional modulator of enhancer activity. Enhancer-gene mapping and eQTLs implicated BLK and FAM167A as targets. The first systematic G×G investigation in BE/EAC, this study uncovers differential risk associations for CDKN2B variation by BLK genotype, suggesting novel biological dependency between two risk loci encoding key mediators of tumor suppression and inflammation.

Commentator Discussion: Esophagectomy may have a role in stage IV esophageal adenocarcinoma.

Commentator Discussion: Esophagectomy may have a role in stage IV esophageal adenocarcinoma.

Therapy response monitoring in blood plasma from esophageal adenocarcinoma patients using cell-free DNA methylation profiling

Esophageal adenocarcinoma (EAC) is an aggressive cancer characterized by a high risk of relapse post-surgery. Current follow-up methods (serum carcinoembryonic antigen detection and PET-CT) lack sensitivity and reliability, necessitating a novel approach. Analyzing cell-free DNA (cfDNA) from blood plasma emerges as a promising avenue. This study aims to evaluate the cost-effective and genome-wide cell-free reduced representation bisulfite sequencing (cfRRBS) method combined with computational deconvolution for effective disease monitoring in EAC patients. cfDNA methylation profiling with cfRRBS was performed on 162 blood plasma samples from 33 EAC cancer patients and 28 blood plasma samples from 20 healthy donors. The estimated tumor fraction for EAC patients at the time of diagnosis was significantly different from the healthy donor plasma samples (one-sided Wilcoxon rank-sum test: p-value = 0.032). Tumor fractions above 15% and focal gains/amplifications in MYC (chr8), KRAS (chr12), EGFR (chr7) and NOTCH2 (chr1) were observed in four samples of distinct patients at the time metastatic disease was detected. This study showed feasibility to estimate tumor fractions in blood plasma of EAC patients based on cfDNA methylation using cfRRBS and computational deconvolution. Nevertheless, in this study only cancer patients with evidence of metastatic disease show high tumor fractions and copy number alterations.

Current status and perspectives of esophageal cancer: a comprehensive review.

Esophageal cancer (EC) continues to be a significant global health concern, with two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Prevention and changes in etiology, improvements in early detection, and refinements in the treatment have led to remarkable progress in the outcomes of EC patients in the past two decades. This seminar provides an in-depth analysis of advances in the epidemiology, disease biology, screening, diagnosis, and treatment landscape of esophageal cancer, focusing on the ongoing debate surrounding multimodality therapy. Despite significant advancements, EC remains a deadly disease, underscoring the need for continued research into early detection methods, understanding the molecular mechanisms, and developing effective treatments.

Advancements and challenges in the treatment of esophageal cancer: A comprehensive review

Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis, ranking seventh in incidence and sixth cancer-related deaths globally. EC is classified in two main types, the esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), with ESCC being more common in Eastern Europe, South Asia, and Africa, while EAC is prevalent in Western Europe and North America. Molecular analysis identifies three subgroups of ESCC, each with distinct genetic mutations and treatment responses. Early-stage EC is often difficult to detect, leading to late-stage diagnoses that necessitate systemic drug therapies, including molecular-targeted therapies and immunotherapies. Immunotherapy, particularly immune checkpoint inhibitor, has shown promising results in improving survival rates for metastatic or persistent EC. It is particularly important to target to multidisciplinary combination therapies, integrating surgery, chemoradiotherapy, targeted therapy and immunotherapy. Additionally, radioimmunotherapy is being explored for its potential to enhance treatment efficacy, especially in advanced and metastatic tumors. However, the pathological complete response rate to neoadjuvant chemoradiotherapy remains suboptimal, highlighting the need for novel treatment strategies. Future research should focus on optimizing treatment combinations and identifying predictive biomarkers to improve clinical outcomes for EC patients.

Effects of chemoradiotherapy on surface PD-L1 expression in esophageal cancer and its implications for immunotherapy

BackgroundEsophageal cancer has a poor prognosis despite treatment advancements. Although the benefit of neoadjuvant chemoradiotherapy (CRT) followed by adjuvant immunotherapy is evident, the effects of CRT on PD-L1 expression in esophageal cancer are not well understood. This study examines the impact of neoadjuvant CRT on PD-L1 surface expression in esophageal cancer both in vitro and in vivo considering its implications for immunotherapy.MethodsPD-L1 expression dynamics were assessed in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) cell lines (OE-33, FLO-1, KYSE-180) treated with Carboplatin, Paclitaxel, radiotherapy (RT), and CRT. PD-L1 expression was measured by flow cytometry at 48- and 72 hours post-treatment. Temporal changes of surface PD-L1 were further investigated in KYSE-180 cells following RT, up to 168h after treatment. Additionally, PD-L1 expression was analyzed via immunohistochemistry in histological samples from 19 patients (9 EAC, 10 ESCC) treated with neoadjuvant CRT according to the CROSS-scheme.ResultsPD-L1 expression was upregulated the most by Carboplatin, a combination of chemotherapy, or CRT in all cell lines. Higher irradiation doses were more effective in inducing PD-L1 expression, while Paclitaxel alone did not consistently increase PD-L1. The ESCC cell line KYSE-180 showed the highest relative PD-L1 increase. Measurement of PD-L1 kinetics revealed a transient upregulation of surface PD-L1, which peaked at 72 hours post-treatment and subsequently returned to baseline levels by 168 hours. In vivo, data demonstrated no significant PD-L1 expression changes when comparing pre- and post-treatment levels.ConclusionsChemotherapy, RT, and CRT can induce PD-L1 expression in various esophageal cancer cell lines. However, neoadjuvant CRT according to the CROSS protocol does not significantly induce PD-L1 in vivo. Considering the difference in time between pre- and post-therapeutic measurements, these findings suggest that PD-L1 upregulation due to neoadjuvant therapy may be transient in vivo as well. This highlights the potential benefit of administering immunotherapy in a neoadjuvant setting.

Distinct microbiome dysbiosis and epigenetic anomaly in esophageal adenocarcinoma and its underlying Barrett’s esophagus

Interaction between host genotoxic changes and mucosa-associated microbiome (MAM) dysbiosis may have a role in various digestive cancers. We investigated MAM in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) progression sequence and its association with host genotoxic changes. 16S rRNA gene sequencing was performed in three different groups of biopsies from nonneoplastic BE from patients without cancer (N, normal group; n = 47) and with EAC (ADJ, adjacent group; n = 27). Endoscopic biopsies were also obtained from EAC tissues (T, tumor group; n = 22). Results were correlated with TP53 mutation, telomere length and DNA methylation of candidate genes (N33, DPYS, SLC16A12, miR124A3 and miR34bc). Genome-wide DNA methylation examined by reduced representation bisulfite sequencing (RRBS) was available for 32 samples (n = 12 for N, n = 12 for ADJ and n = 22 for T groups). Lower microbial alpha diversity measures were observed in ADJ/T groups relative to N group and associated with higher mean Z score DNA methylation of candidate genes. Specific genera (n = 16) with significant change between ADJ/T groups relative to N group occurred mostly in ADJ group (13/16) and half of them (8/16) were associated with DNA methylation status. Integrated MAM and genome-wide methylation analysis demonstrated that hyper-methylated sites, associated with lower alpha diversity measures dominantly occurred within near the transcription start site, codifying genes were involved in metabolic processes. Our result shows that microbial dysbiosis in EAC mostly occurs in adjacent BE and such dysbiosis was associated with DNA methylation status, offering support for a pathogenic role of interaction between host genotoxic changes and MAM in this tumor type.

Identification of PGC as a Potential Biomarker for Progression from Barrett's Esophagus to Esophageal Adenocarcinoma: A Comprehensive Bioinformatic Analysis.

Background: Barrett's esophagus (BE), with metaplastic columnar epithelium in the lower esophagus, predisposes patients to esophageal adenocarcinoma (EAC). Despite extensive research, mechanisms underlying BE progression to EAC remain unclear, and no validated biomarkers are available for clinical use. Progastricsin/Pepsinogen-C (PGC), an aspartic proteinase linked to maintaining normal epithelial morphology, is often absent in advanced gastrointestinal malignancies. This study comprehensively investigates PGC expression across cancers, particularly in esophageal cancer (ESCA), to clarify its role in BE progression to EAC. Methods: We utilized multiple bioinformatic platforms (TIMER, UALCAN, cBioPortal, GEPIA, STRING, Metascape, and GEO database) to assess PGC expression, genomic alterations, and correlations with clinicopathological features, survival, and immune infiltration. Additionally, using the GEO dataset, we compared non-dysplastic Barrett's esophagus (NDBE) patients with those who progressed to malignancy, identifying differentially expressed genes (DEGs), their interactions, and potential roles in progression. Results: PGC was notably upregulated in various cancers, especially in adjacent normal tissues of ESCA. Genomic amplifications of PGC were linked to improved survival in EAC patients, particularly those with high PGC expression, suggesting a protective role. Moreover, PGC expression positively correlated with favorable immune infiltration, notably B cells and CD8+ T cells. Enrichment analysis of downregulated DEGs revealed significant involvement in key biological processes, specifically in extracellular matrix organization. Among the downregulated DEGs, we identified PGC among the top 10 hub genes, underscoring its role in tissue homeostasis. Conclusions: These findings suggest that PGC could serve as a promising biomarker for predicting the high-risk transformation from BE to EAC, offering new insights into EAC progression and future therapeutic targets.

Emerging molecular phenotypes and potential therapeutic targets in esophageal and gastric adenocarcinoma unearthed by whole genome and transcriptome analyses.

Adenocarcinoma of the esophagus and stomach demands a deeper molecular understanding to advance treatment strategies and improve patient outcomes. Here, we profiled the genome and transcriptome landscape of these cancers, explored molecular characteristics that are undetectable by other sequencing platforms, and analyzed their potential clinical ramifications. Our study employed state-of-the-art integrative analyses of whole genome and transcriptome sequencing on 51 matched tumor and germline samples from 46 patients. Mutations and rearrangements in clinically relevant cancer genes were investigated and correlated with OncoKB, a knowledge-based precision oncology database, to identify treatment implications. Genome-wide signatures and manually curated molecular profiles were also determined. The analyses revealed 90 targetable oncogenic mutations and fusions in 63 % of the patients, including novel NTRK, NRG1, ALK, and MET fusions, and structural variants in cancer genes like RAD51B. Also, molecular signatures associated with mismatch repair and homologous recombination deficiency were elucidated. Notably, we identified CDK12-type genomic instability associated with CDK12 fusions. Our findings support the potential of whole genome and transcriptome sequencing analyses as a comprehensive approach to identify treatment targets in adenocarcinoma of the stomach and the esophagus, and their application in precision oncology.

Minimally Invasive Ivor Lewis Esophagectomy

The two main types of esophageal cancer are squamous cell carcinoma, which comprises the majority of cases world-wide, and adenocarcinoma, which is diagnosed with increasing frequency and now accounts for more than 50% of cases in the western hemisphere. Smoking and alcohol consumption are strongly linked to squamous cell carcinoma, and the most important etiologic risk factor for adenocarcinoma is Barrett's esophagus, which occurs in 10 to 15% of patients with gastro-oesophageal reflux disease. Patients generally present with dysphagia and weight loss, and diagnosis is made via endoscopy and biopsy. The surgical treatment of esophageal cancer is dependent upon the location of the cancer, the depth of invasion, and the presence of lymph node metastasis. Smaller tumors that only involve the mucosal layer of the esophagus may be removed by endoscopic mucosal resection, but larger, more invasive tumors require esophageal resection. Esophagectomy can be approached via the trans-hiatal (Orringer), trans-thoracic (Ivor-Lewis), or three-field (McKeown) techniques, and anastomosis between the stomach and the shortened esophagus is achieved through either a gastric pull up or colonic/jejunal interposition. The addition of neoadjuvant chemotherapy for locally-advanced adenocarcinoma has been shown to increase survival compared with surgery alone, and is the standard treatment in these cases. Here, we present the case of a female patient with dysphagia who was found to have a locally-advanced distal esophageal adenocarcinoma. In this case, a minimally-invasive Ivor Lewis esophagectomy was performed with neoadjuvant chemotherapy.

Strategies for a Biomarker-Driven Approach to Locally Advanced Esophageal Cancer

AbstractTreatment paradigms for esophageal cancer are evolving and there is a growing need for prognostic and predictive biomarkers to guide clinical decision making. Perioperative chemotherapy has emerged as a standard of care for esophageal adenocarcinoma (EAC), yet some patients with an elevated local recurrence risk or poor tolerance to intensified chemotherapy may benefit from neoadjuvant therapy including radiation. Biomarkers for predicting treatment response to radiation, chemotherapy, and immunotherapy in other gastrointestinal malignancies and solid tumors are emerging that could be used to personalize treatment approaches. Recent trials have demonstrated the safety and efficacy of a watch-and-wait approach for both EAC and esophageal squamous cell carcinoma, but with pathologic complete response rates ranging from 10 to 49% it will be critical to improve patient selection for omission of surgery. Further prospective study is warranted to evaluate the clinical efficacy of a biomarker-driven treatment approach.

Real-World Clinical Utility of a Methylated DNA Biomarker Assay on Samples Collected with a Swallowable Capsule-Balloon for Detection of Barrett's Esophagus (BE).

Background: Barrett's Esophagus (BE) is the only known precursor for esophageal adenocarcinoma (EAC). Patients with multiple risk factors for BE/EAC are recommended for screening; however, few eligible patients undergo evaluation by endoscopy. EsoGuard® (EG) is a commercially available biomarker assay used to analyze esophageal cells collected non-endoscopically with EsoCheck® (EC) for the qualitative detection of BE/EAC. This study evaluates the real-world clinical utility of EG on cells collected with EC in patients defined by U.S. gastroenterology societies to be at-risk for BE and EAC. Methods: This multi-center, observational CLinical Utility of EsoGuard (CLUE) study enrolled screening-eligible patients as defined by the American College of Gastroenterology (ACG) and the American Gastroenterological Association (AGA). Clinical utility was evaluated by the provider decision impact of EG and additionally by assessing patient compliance outcomes with recommended follow-up testing. Results: There were 551 patients enrolled, with a mean age of 62.0 ± 12.4 years and 56.1% (309/551) meeting ACG guideline criteria for BE screening. EC cell collection was successful in 97.1% (535/551), among which the EG positivity rate was 27.3% (n = 146). The provider decision impact was high, with 100% of EG-positive patients being referred for esophagogastroduodenoscopy (EGD), while 98% of EG negative patients were not referred. Among the EG-positive patients, the overall compliance with follow-up EGD was 85.4%. Conclusions: Combining EC non-endoscopic esophageal cell collection with the EG biomarker assay is effective in guiding provider decision-making for the detection of BE and EAC. Patients with positive EG results demonstrate high compliance with recommended follow-up EGD.

A Simple Morphometric Analysis of Preoperative Therapy Response for Esophageal Adenocarcinoma.

Histologic assessment of tumor regression grade (TRG) on esophagogastrectomy specimens after neoadjuvant therapy is an excellent predictor of local recurrence rate and long-term survival in esophageal adenocarcinomas. Although several grading systems exist globally, the modified Ryan system suggested by the College of American Pathologists (CAP) is widely used in North America. Most systems rely on quantitative percentage estimation of the residual tumor with or without additional qualitative descriptors, which is relatively subjective with poor interobserver agreement. To test a morphometric-based approach using the microscopic objective lens to estimate the size of the largest focus of the residual tumor. A total of 69 esophageal specimens post neoadjuvant therapy were evaluated. Tumor size was morphometrically determined by the microscopic field, using an Olympus microscope with ×10/×22 eyepieces. Residual viable tumor was categorized into 4 groups, using ×2, ×4, and ×10 objectives: less than or equal to an ×10 field; larger than an ×10 field but less than or equal to an ×4 field; larger than an ×4 field but less than an ×2 field; and larger than or equal to an ×2 field. Morphometric measurements significantly correlated with the CAP treatment effect scores. There was no significant difference in overall survival between larger than or equal to ×2 and ×2 to ×4 groups; however, a 3-tier system (TRG1: ≤ ×10, TRG2: > ×10 and ≤ ×4, and TRG3: > ×4) showed significant survival differences (P = .01). Significant differences in the percentage of lymphovascular and perineural invasion, advanced TNM stage, and lymph node metastasis were identified among the 3 groups. The proposed 3-tier morphometric approach based on microscopic field size is a simple and easy-to-use method, which helps stratify patients into 3 groups with distinct histopathologic features and overall survival.