Esophageal Adenocarcinoma Research Articles

S663 Investigating the Risk Factors for Recurrence of T1B Esophageal Adenocarcinoma After Esophagectomy: A Long-Term Follow-Up Retrospective Study

S663 Investigating the Risk Factors for Recurrence of T1B Esophageal Adenocarcinoma After Esophagectomy: A Long-Term Follow-Up Retrospective Study

Risk of cardiac arrhythmias and outcomes with perioperative FLOT vs CROSS regimens for esophageal adenocarcinoma

Risk of cardiac arrhythmias and outcomes with perioperative FLOT vs CROSS regimens for esophageal adenocarcinoma

Revolutionizing Early Detection: The Influence of Machine Learning in Esophageal Adenocarcinoma Diagnosis

Machine learning is an analysis technique of big data that uses computers and mathematical models to develop algorithms. These algorithms are applied in many situations and one of the most common uses is in developing prediction models. Machine learning is the activity of making prognosis of other data points which are related to the self using key factors from a dataset. It is designed to effectively predict the dysplasia within a given setting using machine learning algorithms on a dataset with primary focus on Barrett’s Esophagus. The study investigates the use of five classification methods: As per the classification, the techniques identified include Naïve Bayes, Support Vector Machine (SVM), Decision Tree, K-Nearest Neighbors, and Logistic Regression. Barrett’s Esophagus Below are the methods applied using and without Principal Component Analysis (PCA) on the special dataset of Barrett’s esophagus. The primary objective is the identification of the effectiveness of each algorithm by comparing their functional characteristics such as F1 score, recall value, accuracy percentage, precision ratio, and specificity coefficient. From the results obtained from the experiments, two algorithms that yield good accuracy for predicting Barrett’s esophagus in this dataset are the SVM algorithm with PCA and Logistic Regression algorithm with PCA and both algorithms returned review ratings of 1. undefined This career has earned a maximum Score of 0.1000, Naïve Bayes perform well in the assessment with 0.964 of accuracy, it followed by K-Nearest Neighbors with 0.9349 and Logistic Regression with 0.923.

P53 mutation biases squamocolumnar junction progenitor cells towards dysplasia rather than metaplasia in Barrett’s oesophagus

BackgroundWhile p53 mutations occur early in Barrett’s oesophagus (BE) progression to oesophageal adenocarcinoma (EAC), their role in gastric cardia stem cells remains unclear.ObjectiveThis study investigates the impact of p53 mutation...

Evaluating the feasibility and predictive accuracy of biodynamic imaging to platinum-based chemotherapy response in esophageal adenocarcinoma.

Esophageal cancer management lacks reliable response predictors to chemotherapy. In this study we evaluated the feasibility and accuracy of Biodynamic Imaging (BDI), a technology that employs digital holography as a rapid predictor of chemotherapy sensitivity in locoregional esophageal adenocarcinoma. Pre-treatment endoscopic pinch biopsies were collected from patients with esophageal adenocarcinoma during standard staging procedures. BDI analyzed the tumor samples and assessed in vitro chemotherapy sensitivity. BDI sensitivity predictions were compared to patients' pathological responses, the gold standard for determining clinical response, in the surgically treated subset (n=18). BDI was feasible with timely tissue acquisition, collection, and processing in all 30 enrolled patients and successful BDI analysis in 28/29 (96%) eligible. BDI accurately predicted chemotherapy response in 13/18 (72.2%) patients using a classifier for complete, marked, and partial/no-response. BDI technology had 100% negative predictive value for complete pathological response hence identifying patients unlikely to respond to treatment. BDI technology can potentially predict patients' response to platinum chemotherapy. Additionally, this technology represents a promising step towards optimizing treatment strategies for esophageal adenocarcinoma patients by pre-emptively identifying non-responders to conventional platinum-based chemotherapy.

Mechanistic Insights on Microbiota-Mediated Development and Progression of Esophageal Cancer

Esophageal cancer (EC) is one of the most common malignant tumors worldwide, and its two major types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), present a severe global public health problem with an increasing incidence and mortality. Established risk factors include smoking, alcohol consumption, and dietary habits, but recent research has highlighted the substantial role of oral microbiota in EC pathogenesis. This review explores the intricate relationship between the microbiome and esophageal carcinogenesis, focusing on the following eight significant mechanisms: chronic inflammation, microbial dysbiosis, production of carcinogenic metabolites, direct interaction with epithelial cells, epigenetic modifications, interaction with gastroesophageal reflux disease (GERD), metabolic changes, and angiogenesis. Certain harmful bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are specifically implicated in sustaining irritation and tumor progression through pathways including NF-κB and NLRP3 inflammasome. Additionally, the review explores how microbial byproducts, including short-chain fatty acids (SCFAs) and reactive oxygen species (ROS), contribute to DNA harm and disease advancement. Furthermore, the impact of reflux on microbiota composition and its role in esophageal carcinogenesis is evaluated. By combining epidemiological data with mechanistic understanding, this review underscores the potential to target the microbiota–immune system interplay for novel therapeutic and diagnostic strategies to prevent and treat esophageal cancer.

Comparing the prognosis of esophageal adenocarcinoma with bone and liver metastases: A competing risk analysis.

About half of the patients with esophageal cancer are presenting with metastasis at initial diagnosis. However, few studies have concerned on the prognostic factors of metastatic esophageal adenocarcinoma (mEAC). This research aimed to investigate the effects of single bone metastasis (BM) and single liver metastasis (LM) on prognosis of mEAC patients. Data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database. We compared the effects of LM and BM on overall survival (OS), EAC-specific survival (CSS), and EAC-specific death (EASD) by multivariate Cox regression, Kaplan-Meier analysis, and competing risk regression models. A total of 1,278 EAC patients were recruited in this study. Of which 78.95% (1009/1278) were EASD, and 12.68% (162/1278) were non-EAC-specific death (non-EASD). In multivariate Cox regression analysis, surgery, chemotherapy, and AJCC.T2 (vs. T1) were identified as protective factors for OS&CSS, while divorced/separated, single/unmarried (vs. married), grade III-IV (vs. grade I-II) and BM (vs. LM) were identified as risk factors. Competing risk regression analysis further confirmed that surgery and chemotherapy were beneficial to the patients with mEAC, and BM (vs. LM) was a risk factor for mEAC patients when considering the existence of the competitive risk events. Our study indicated that mEAC patients with BM face a worse prognosis compared to those with LM. Additionally, surgery and chemotherapy emerge as protective factors for mEAC patients. These findings offer evidence-based insights for clinical management and contribute to the field.

MERTK Inhibitor Associated Retinal Toxicity in a Human.

The MER proto-oncogene tyrosine kinase (MERTK) helps maintain the homeostasis of the retinal pigmented epithelium (RPE). Additionally, MERTK regulates the innate immune system. As such inhibition of MERTK has gained recent interest as a target for cancer therapeutics. Herein, we present on MERTK inhibitor associated retinal toxicity in a human. A 43-year-old male with past medical history of esophageal adenocarcinoma was enrolled in a trial studying the MERTK inhibitor PF-07265807. As part of the study protocol, the patient was seen every two to three weeks for dilated fundus exams and ancillary testing. Data on the patient's relevant past medical history, ophthalmic exam findings, and imaging performed at baseline and subsequent ophthalmology visits was obtained via retrospective chart review. At the patient's baseline visit, his dilated exam and testing were normal. Seven months after starting the MERTK inhibitor the patient developed subtle but reproducible signs of retinal toxicity with disruption of the extrafoveal ellipsoid zone on optical coherence tomography and extrafoveal hyper-autofluorescence on short wavelength fundus autofluorescence. The patient's vision remained stable throughout the study; however, the medication was stopped due to the unknown ocular effects as well as progression of the patient's cancer. Patients taking MERTK inhibitors should be monitored by an ophthalmologist while on the drug. If toxicity develops, discussion of whether to continue the medication should take place between the patient, ophthalmologist, and oncologist, with consideration of the risks of vision loss versus benefits of taking the medication from a cancer perspective.

Exploring the incidence of dysplasia or adenocarcinoma in early onset Barrett's esophagus.

Currently data on the risk of progression to and lifetime risk of cancer are not available for patients with young onset Barrett's esophagus (BE). Our aim was to obtain epidemiologic data on the incidence of dysplasia or adenocarcinoma in young onset BE in the Netherlands by collecting data on all histologically confirmed cases over a prolonged period of 25 years between January 1, 1991 and December 31, 2015. Data were obtained from the Dutch National Pathology Registry. Patients were included if there was a suspicion of BE visualized in the esophagus during the endoscopic examination in combination with a concordant histologic diagnosis of intestinal metaplasia. 231 patients with early onset BE were identified (median age 26 years [range 0-29 years]), with 17 progressing to dysplasia (6 prevalent and 11 incident). For the patients with incident dysplasia, the median surveillance time between the diagnosis of early onset BE and diagnosis of dysplasia was 5 years (range 0-16 years). The incidence rate of dysplasia was 7.3 per 1000 person-years. There were three patients who developed adenocarcinoma (1 prevalent and 2 incident), who were diagnosed at ages 28, 35, and 36 years. The incidence rate of adenocarcinoma was 1.3 per 1000 person-years. In this 25-year period, 231 patients were diagnosed with early onset BE in the Netherlands, with 17 patients progressing to dysplasia and three developing adenocarcinoma. This corresponded to incidence rates of 7.3 per 1000 person-years for dysplasia and 1.3 per 1000 person-years for adenocarcinoma.

Lactate Suppresses Growth of Esophageal Adenocarcinoma Patient-Derived Organoids through Alterations in Tumor NADH/NAD+ Redox State.

Barrett's esophagus (BE) is a common precancerous lesion that can progress to esophageal adenocarcinoma (EAC). There are significant alterations in the esophageal microbiome in the progression from healthy esophagus to BE to EAC, including an increased abundance of a variety of lactate-producing bacteria and an increase of lactate in the tumor microenvironment, as predicted by metabolic modeling. The role of bacterial lactate in EAC is unknown. Here, we utilize patient-derived organoid (PDO) models of EAC and demonstrate that lactate inhibits the growth and proliferation of EAC PDOs through alterations in the tumor NADH/NAD+ redox state. Further RNA sequencing of EAC PDOs identifies ID1 and RSAD2 as potential regulatory molecules crucial in mediating lactate's ability to suppress glycolysis and proliferation. Gene ontology analysis also identifies the activation of inflammatory and immunological pathways in addition to alterations in the metabolic pathways in EAC PDOs exposed to lactate, suggesting a multi-faceted role for lactate in the pathogenesis of EAC.

Outcomes of patients with Barrett's oesophagus with low-grade dysplasia undergoing endoscopic surveillance in a tertiary centre: a retrospective cohort study.

Barrett's oesophagus predisposes individuals to oesophageal adenocarcinoma (OAC), with the risk of progression to malignancy increasing with the degree of dysplasia, categorized as either low-grade dysplasia(LGD) or high-grade dysplasia (HGD). The reported incidence of progression to OAC in LGD ranges from 0.02% to 11.43% per annum. In patients with LGD, Australian guidelines recommend 6-monthly endoscopic surveillance. We aimed to describe the surveillance practices within a tertiary centre, and to determine the predictive value of surveillance as well as other risk factors for progression. Endoscopy and pathology databases were searched over a 10-year period to collate all cases of Barrett's oesophagus with LGD. Medical records were reviewed to document patient factors and endoscopic and histologic details. Because follow-up times varied greatly, survival analysis techniques were employed. Fifty-nine patients were found to have LGD. Thirteen patients (22.0%) progressed to either HGD or OAC (10 (16.9%) and three (5.1%) respectively); the annual incidence rates of progression to HGD/OAC and OAC were 5.5% and 1.1% respectively. All patients who developed OAC had non-guideline-adherent surveillance. A Cox model found only two predictors of progression: (i) guideline-adherent surveillance, performed in 16 (27.1%), detected progression to HGD/OAC four times earlier than non-guideline-adherent surveillance (95% confidence interval (CI) = 1.3-12.3; P = 0.016). (ii) The detection of visible lesions at exit endoscopy independently predicted progression (hazard ratio = 6.5; 95% CI = 1.9-22.8; P = 0.003). Barrett's oesophagus with LGD poses a significant risk of progression to HGD/OAC. Guideline-recommended surveillance is effective, but is difficult to adhere to. Clinical predictors for those who are more likely to progress are yet to be defined.

ADAR promotes USP38 auto-deubiquitylation and stabilization in an RNA editing–independent manner in esophageal squamous cell carcinoma

Esophageal cancer is mainly divided into esophageal adenocarcinoma (EADC) and esophageal squamous cell carcinoma (ESCC). China is one of the high-incidence areas of esophageal cancer, of which about 90% are ESCC. The deubiquitinase USP38 has been reported to play significant roles in several biological processes, including inflammatory responses, antiviral infection, cell proliferation, migration, invasion, DNA damage repair, and chemotherapy resistance. However, the role and mechanisms of USP38 in ESCC development remain still unclear. Furthermore, although many substrates of USP38 have been identified, few upstream regulatory factors of USP38 have been identified. In this study, we found that USP38 was significantly upregulated in esophageal cancer tissues. Knockdown of USP38 inhibited ESCC growth. USP38 stabilized itself through auto-deubiquitylation. In addition, we demonstrate that ADAR could enhance the stability of USP38 protein and facilitate USP38 auto-deubiquitylation by interacting with USP38 in an RNA editing-independent manner. ADAR inhibition of ESCC cell proliferation depended on USP38. In summary, these results highlight that the potential of targeting the ADAR-USP38 axis for ESCC treatment.

Real-world evaluation of multimodal treatment practice in older oesophageal cancer patients.

Elderly-specific data for multimodal treatment of oesophageal cancer (EC) is lacking. This study aimed to evaluate the safety and efficacy of multimodal treatment in older EC patients and to compare the impact of neoadjuvant chemotherapy (NCT) and neoadjuvant chemoradiotherapy (NCRT). Patients diagnosed with oesophageal squamous cell carcinoma or adenocarcinoma who received NCT/NCRT were identified in the National Cancer Database (NCDB, 2004-2015). First, we compared baseline and post-treatment characteristics between younger (<70 years) and older patients (≥70 years). Logistic regression was used to investigate risk factors of postoperative mortality. Second, we evaluated the effect of neoadjuvant chemotherapy on postoperative mortality and overall survival in the older cohort. Inverse probability of treatment weights and multivariable analyses were used to compensate for differences in baseline covariates. We 1st compared outcomes of neoadjuvant therapy plus oesophagectomy in 14778 eligible EC patients. The older group experienced higher rates of postoperative mortality at 30 days (5.8%) and 90 days (13.5%) compared to younger patients. Postoperative mortality was significantly related to the Charlson-Deyo score and treatment-related factors including neoadjuvant therapy type and minimally invasive technique. Second, among the 3141 older patients (with a median follow-up of 57.8 months and 2029 deaths), those receiving NCT obtained significantly lower postoperative mortality and improved overall survival compared with NCRT (inverse probability of treatment weights-adjusted P = 0.05; hazard ratio 0.85; 95% Cl 0.72-0.99). Neoadjuvant therapy plus oesophagectomy carries increased short-term mortality risk in older EC patients. NCT in older EC patients showed lower postoperative mortality but no statistically significant differences in overall survival, with a point estimate favouring NCT compared to the NCRT group, making NCT a potential option for consideration in specific cases.

Inhibition of Insulin-like Growth Factor 1 Receptor/Insulin Receptor Signaling by Small-Molecule Inhibitor BMS-754807 Leads to Improved Survival in Experimental Esophageal Adenocarcinoma.

The insulin-like growth factor-1 (IGF-1) and insulin axes are upregulated in obesity and obesity-associated esophageal adenocarcinoma (EAC). Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a contemporary nanotechnology-based paclitaxel (PT) bound to human albumin, ensuring its solubility in water rather than a toxic solvent. Here, we examined the benefits of inhibiting insulin-like growth factor-1 receptor/insulin receptor (IGF-1/IR) signaling and the enhancement of nab-paclitaxel effects by inclusion of the small-molecule inhibitor BMS-754807 using both in vitro and in vivo models of EAC. Using multiple EAC cell lines, BMS-754807 and nab-paclitaxel were evaluated as mono and combination therapies for in vitro effects on cell proliferation, cell death, and cell movement. We then analyzed the in vivo anticancer potency with survival improvement with BMS-754807 and nab-paclitaxel mono and combination therapies. BMS-754807 monotherapy suppressed in vitro cell proliferation and wound healing while increasing apoptosis. BMS-754807, when combined with nab-paclitaxel, enhanced those effects on the inhibition of cell proliferation, increment in cell apoptosis, and inhibition of wound healing. BMS-754807 with nab-paclitaxel produced substantially greater antitumor effects by increasing in vivo apoptosis, leading to increased mice survival compared to those of BMS-754807 or nab-paclitaxel monotherapy. Our outcomes support the use of BMS-754807, alone and in combination with nab-paclitaxel, as an efficient and innovative treatment choice for EAC.

Local Invasion Patterns Characterized by SARIFA and Tumor Budding Differ and Have Distinct Prognostic Significance in Esophageal Adenocarcinoma and Squamous Cell Carcinoma.

Both esophageal squamous cell carcinoma (ESQCC) and adenocarcinoma (EAC) are known to have poor prognosis. We aimed to investigate the invasion front areas of 57 ESQCC and 43 EAC cases to find histological signs of metastatic progression. Tumor cell clusters with different cell counts, including tumor buds (TBs) and poorly differentiated clusters (PDCs), were assessed. The presence of the recently described Stroma AReactive Invasion Front Area (SARIFA) phenomenon, which defines a direct contact between tumor cells and adipocytes, was more frequently observed in EAC than in ESQCC (p = 0.004). In adenocarcinomas, a higher prevalence of SARIFA was observed in tumors with a higher number of small clusters (TBs and small PDCs; p < 0.001); furthermore, both the high number of TBs (p = 0.016) and the presence of SARIFA (p = 0.001) correlated with a higher pT stage. SARIFA positivity in EAC (p = 0.011) and high TB in ESQCC (p = 0.0006) were found to be independent prognostic factors for lymph node metastases. Moreover, in ESQCC, the higher absolute number of both TBs and PDCs was associated with shorter overall survival (p = 0.0269 and p = 0.0377, respectively). Our results suggest that the histological subtypes of esophageal cancer behave differently, namely, that different features of the invasion front are of prognostic significance.

A rare esophageal metastatic adenocarcinoma misdiagnosed as esophageal leiomyoma.

Here we report for the first time an extremely rare case of esophageal metastatic adenocarcinoma resembling esophageal leiomyoma leading to misdiagnosis. The case gives us great insights that in any esophageal stenosis with normal mucosa, metastasis must be contemplated as a differential diagnosis, especially in patients with a history of cancer.

Gluteal metastasis on both sides from Esophageal Carcinoma

Hematogenous metastasis of esophageal carcinoma is not uncommon however esophageal carcinoma metastasis to skeletal muscles is a rare entity. Here, we report the case of metastasis in gluteus muscles on both the sides in a known case of Ca Esophagus (Adenocarcinoma). Early diagnosis of the possibility of metastasis in muscles in a cancer patient can increase the life expectancy and can reduce the rate of complications.

Bioinformatic Analysis of IKK Complex Genes Expression in Selected Gastrointestinal Cancers.

Gastrointestinal cancers account for over a quarter of all cancer cases and are associated with poor prognosis and high mortality rates. The IKK complex (the canonical I kappa B kinase), comprising the CHUK, IKBKB, and IKBKG genes, plays a crucial role in activating the NF-kB signaling pathway. This study aimed to analyze publicly available bioinformatics data to elucidate the oncogenic role of IKK genes in selected gastrointestinal cancers. Our findings reveal that IKBKB and IKBKG are significantly upregulated in all examined cancers, while CHUK is upregulated in esophageal carcinoma and stomach adenocarcinoma. Additionally, the expression of IKK genes varies with histological grade and nodal metastases. For instance, in stomach adenocarcinoma, CHUK and IKBKB are upregulated in higher histological grades and greater lymph node infiltration. Lower expression levels of CHUK, IKBKB, and IKBKG in stomach adenocarcinoma and IKBKB in esophageal squamous cell carcinoma correlate with shorter overall survival. Conversely, in esophageal adenocarcinoma, reduced IKBKG expression is linked to longer overall survival, while higher IKBKB expression in colon adenocarcinoma is associated with longer overall survival. Given the significant role of IKK genes in the development and progression of selected gastrointestinal cancers, they hold potential as prognostic markers and therapeutic targets, offering valuable insights for clinical practice.

Analytical Validation of Esopredict, an Epigenetic Prognostic Assay for Patients with Barrett's Esophagus.

EsopredictTM is a prognostic assay that risk-stratifies Barrett's esophagus patients to predict future progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). Established based on foundational studies at Johns Hopkins University, a risk algorithm was developed and clinically validated in two independent studies (n = 320). EsopredictTM is currently offered as a clinical test under the Clinical Laboratory Improvement Amendments (CLIA) guidelines. Here we present the analytical validation by repeated testing of FFPE tissues (n = 26 patients), cell lines, and contrived DNA controls to determine assay performance regarding analytical sensitivity (as defined by the limit of detection (LOD)), analytical specificity (as defined by the limit of blank (LOB)), accuracy as determined from the average positive and negative agreement, repeatability, and reproducibility. The LOD for the assay at 1.5% DNA methylation was significantly higher than the LOB, as determined by an unmethylated DNA control (0% methylated DNA). Inter- and intra-assay average positive agreement (APA) were 88% and 94%, respectively, while average negative agreement (ANA) values were 90% and 94%, respectively. Average inter- and intra-assay precision were <9% and <5% coefficient of variation (CV), respectively. These results confirm that EsopredictTM is a highly reproducible, sensitive, and specific risk categorization assay for the prediction of progression to HGD or EAC within 5 years.

EP146 - Feasibility Study: SmartWatch and Rockport Walk Test safely measures estimated VO2 Max

Abstract Aims To assess feasibility and safety of estimating VO2 max using a SmartWatch and the Rockport Walk Test, and to assess robustness of the protocol for a pilot study on oesophageal adenocarcinoma patients. Methods This prospective feasibility study included ASA grade 1 adults with a SmartWatch. Participants walked 1 mile on the flat, and end heart rate and time taken were recorded both via SmartWatch and manually. Pre- and post-exercise questionnaires provided. Estimated VO2 calculated using the Rockport formula. Results Ten participants (five female), mean age 32.8 (25-37). Mean heart rate via SmartWatch 107.25bpm (80-133) and manually 104.6bpm (84-120). Mean time to complete 1 mile 15:17 minutes (13:08 – 16:48). Average estimated VO2 max 43.6 (41.57- 50.03). Pre-activity 100% of participants found instructions clear and easy-to-follow, and were confident to undertake the activity and complete it safely. Although pre-activity 20% of participants were not confident in finding a suitable flat location and 10% not confident with the technology, in the post-activity survey 100% of participants found it easy to find a suitable location and easy to measure, record and upload their results. One user highlighted difficulty with manually measuring heart rate, and another noted challenges with road crossings disrupting their walk. Conclusions It is feasible to measure estimated VO2 max remotely using wearable technology and a validated test such as Rockport Walk Test in healthy adults. This study highlighted several areas of protocol improvement to deploy the study in oesophageal cancer patients to minimise potential risks and optimise safety and usability.